5% in 2007 to 48.5% in 2012. However the prevalent patients remaining on peritoneal dialysis dropped from 91.4% in 2007 to 66.9% in 2012, amounting

to drop of 24.5%. Among the causes that lead to downward trend during the above period was that more patients were being transplanted accounting to 16.1% in 2012 compared to 6.1% in 2007 followed by other causes like being palliated, infection and transferred to haemodialysis and other centres. Conclusion: The results of our study showed that although the incident patients entering the peritoneal dialysis programme increased, there is a downward trend in patients remaining on peritoneal dialysis at our centre as more patients are being transplanted Rapamycin and palliated. 250 OPTIMISING PAEDIATRIC DIALYSIS: A COMPARISON OF ADAPTED AND CONVENTIONAL PERITONEAL DIALYSIS L SHAW1, Z MILLARD1, C QUINLAN1,2 1The Royal Children’s Hospital, Melbourne, Victoria; 2The Murdoch Children’s Research Institute, Melbourne, Victoria, Australia Aim: To compare the efficacy of Conventional peritoneal dialysis (Con-PD) and Adapted PD (Ad-PD) in children. Background: Con-PD is delivered as a series of identical exchanges. Ad-PD consists of several initial

short, low volume cycles, followed by several long, higher volume cycles. A recent randomised trial by Fischbach et al. showed significantly increased ultrafiltration (UF) and greater clearance of urea, creatinine and phosphate

https://www.selleckchem.com/products/MK-2206.html with lower metabolic cost as measured by glucose absorption in a trial in 19 adults. Methods: Patients are randomised to 6 weeks of Ad-PD followed by 6 weeks of Con-PD or vice versa. All patients are seen 2-weekly for clinical assessment and assessment of dialysis adequacy using electrolyte samples of blood, urine and dialysate. Results: This is an ongoing study, to date 9 children have been recruited and 3 have commenced Ad-PD. The first 2 were low transporters and were withdrawn in the first week due to CYTH4 a clinically significant decrease in UF volume. The third child was a high transporter and had a significant increase in UF (from 100 to 400 mL) and a significant decrease in phosphate and potassium, such that supplementation was commenced. We await the full results which will be presented at the meeting. Conclusion: The results of the adults Ad-PD trial were very encouraging but the initial results from our study, the first paediatric trial of Ad-PD, show that it does not work for every child. However the child that had increased UF was failing Con-PD with consideration of haemodialysis and thus this has been an excellent result for her. It is possible that outcomes are dependent on transporter status but further results are necessary to confirm this initial finding.

S2). In addition, IFN-γ production by naive T cells incubated with C. neoformans-pulsed eosinophils was similar to controls (Fig. 8a).

However, the production of TNF-α by these cells showed a significant increase in the presence of C. neoformans-pulsed or unpulsed eosinophils (Fig. 8b). Finally, we decided to investigate which T-cell population (CD4+ or CD8+) was involved in the production of IFN-γ and TNF-α. Surprisingly, only C. neoformans-primed CD8+ T cells cultured with C. neoformans-pulsed eosinophils produced IFN-γ. However, when both primed CD4+ T cells and CD8+ T cells were incubated with C. neoformans-pulsed eosinophils, large amounts of IFN-γ and TNF-α were produced (Fig. 8c,d). These results suggest that cooperation between C. neoformans-primed CD4+ and CD8+ T cells is very important in the case of IFN-γ and BAY 80-6946 manufacturer necessary for TNF-α production in the presence of C. neoformans-pulsed eosinophils. C. neoformans-pulsed eosinophils not only stimulated the proliferation of C. neoformans-primed

CD4+ and CD8+ T cells, but also produced a Th1 microenvironment where cooperation between these two T-cell populations could take place. This study provides the first evidence that rat eosinophils are capable of phagocytosing and presenting C. neoformans antigens to primed T cells, which then trigger a fungal-specific Th1 immune response. Eosinophils have been shown to be components of the inflammatory response to C. neoformans infection in the rat lung,3 and we have previously MK-8669 observed the presence of a large Casein kinase 1 number of eosinophils in the granulomas surrounding C. neoformans-encapsulated

yeasts during disseminated cryptococosis in rats (unpublished data). Moreover, although rat peritoneal eosinophils are unable to significantly phagocytose C. neoformans in vitro in the absence of opsonizing antibody, initial phagocytosis is rapidly completed in the presence of a specific mAb as an opsonin.19 Eosinophils constitutively express a variety of Fc receptors, including FcγRII, FcεRII and FcαR, with this expression varying according to the cytokine stimulation. Cross-linking of Fc receptors results in a variety of effects, including the induction of cytotoxicity, phagocytosis, immune complex binding and respiratory burst.19 Herein, we have demonstrated that eosinophils phagocytose opsonized live yeasts of C. neoformans and that this phenomenon involves the engagement of FcγRII and CD18, because the blocking of these receptors together caused the almost complete inhibition of fungal phagocytosis. These results are in agreement with previous reports which showed that Mφ and dendritic cells take up C. neoformans yeasts and the capsular polysaccharide via FcγRII and CD18.23,25,31,32 Furthermore, our results demonstrate that the phagocytosis of opsonized C.

The largest increases were observed for GBP5 (291-fold), GBP4 (102-fold), GBP2 (22-fold) and GBP1 (14-fold) in ASC cultured with proinflammatory cytokines (Fig. 2b). In addition, ASC cultured with proinflammatory cytokines strongly up-regulated the expression of myxovirus resistance genes 1 (19-fold) and 2 (10-fold) (Fig. 2c). This increase in expression was not observed in ASC cultured with MLR. Although ASC can exert immunosuppressive activity, they also express genes for proinflammatory factors (Fig. 2d). IL-6 was expressed

https://www.selleckchem.com/products/MLN8237.html highly under all culture conditions. After exposure of ASC to alloactivated PBMC, we found a 46-fold up-regulation of IL-8, while the expression of IL-1β (sevenfold) and IL-33 (11-fold) also increased. In contrast, culture of ASC with proinflammatory cytokines up-regulated the expression of TNF superfamily (TNFSF) member 10 and member 13B by factors 53 and 11, respectively. ASC did not express IL-2. Serum amyloid A1 and A2, factors produced by the liver in response to inflammatory stimuli, showed strongly increased gene expression after culture of ASC with alloactivated PBMC (31-fold and 20-fold, respectively)

(Fig. 2e), while these factors were not up-regulated in ASC cultured with proinflammatory cytokines. ASC expressed high levels of HLA class I, whereas HLA class II levels were low under control conditions (Fig. 2f,g). In the presence of alloactivated PBMC, HLA class I expression by ASC was increased Doxorubicin molecular weight slightly (twofold) and HLA class II expression did not change significantly. In contrast, ASC cultured with proinflammatory cytokines up-regulated the expression of HLA class I genes up to sixfold and HLA class II up to 144-fold. Next, the effect of inflammatory conditions on the chemoattractive properties of ASC was examined. Culture of ASC click here with MLR or proinflammatory cytokines induced differential expression of several chemokines. ASC cultured with MLR increased the expression of the neutrophil,

monocyte and eosinophil attractants CXCL1 (18-fold) and CXCL6 (21-fold) (Fig. 2h). ASC cultured with proinflammatory cytokines showed strong increases in the expression of the T lymphocyte attractants CXCL9 (209-fold), CXCL10 (522-fold) and CXCL11 (251-fold), whereas the neutrophil, monocyte and eosinophil attractants CXCL1 and CXCL6 showed weaker increases (sevenfold and ninefold). Chemokines of the CCL-motive were also induced specifically by ASC depending on the inflammatory stimulus (Fig. 2i). In ASC cultured with MLR the expression of CCL2 (fourfold), CCL5 (sevenfold), CCL13 (sixfold), CCL20 (eightfold) and CCL28 (threefold) was increased significantly compared to control ASC. Culture of ASC with the proinflammatory cytokines strongly increased the expression of CCL2 (fivefold), CCL5 (27-fold), CCL7 (17-fold), CCL8 (41-fold) and CCL13 (12-fold), but had no effect on the lymphocyte attractants CCL20 and CCL28.

Therefore, the foci stained by anti-SMN antibody have been designated

as Gemini of the Cajal body, or Gems. PF-01367338 However, coilin and SMN are colocalized in most of the cell. Therefore, these bodies are indistinguishable in most cell types.[30] It has been reported that Gems are partly colocalized with TDP-43 bodies in cultured cells.[9] In human spinal motor neurons, some Gems are stained with TDP-43, but not all of them.[34] In addition, the depletion of TDP-43 decreases the number of Gems in HeLa cells and mouse spinal motor neurons.[34, 35] A decrease in the number of Gems is also observed in spinal muscular atrophy.[36] Thus, we hypothesized that the loss of nuclear TDP-43 may result in a decrease in the number of Gems in spinal motor neurons with ALS as well. Indeed, our group and others have found that the number of Gems decreased in spinal motor neurons with ALS.[34, 37] However, surprisingly we found that the number of Gems was decreased in spinal motor neurons that still contained nuclear TDP-43.[34] This result raises the possibility that

the decreasing number of Gems precedes the alteration of TDP-43. However, in spinal motor neurons with spinal muscular atrophy, no alteration of TDP-43 has been reported, suggesting that the alteration of TDP-43 precedes the decrease in the number of Gems. Therefore, we propose that disturbance of a function of TDP-43 associated with the formation of Gems precedes the disappearance of TDP-43 from the nucleus (Fig. 1a–c). Accumulating

evidence suggests that Cyclooxygenase (COX) the disappearance of nuclear TDP-43 precedes the inclusion formation of TDP-43 (Fig. 1d,e).[14] Although click here the mechanism for the disappearance of nuclear TDP-43 is unclear, the dysfunction of TDP-43 might precede their disappearance from the nucleus. Research has shown that TDP-43 regulates its own amounts of product by affecting its own mRNA.[18, 38] Thus, the decreasing amount of nuclear TDP-43 should induce the production of more TDP-43. However, in spinal motor neurons with ALS, nuclear TDP-43 disappears. Therefore, these cells lose TDP-43 function, which is associated with pre-mRNA splicing, including the autoregulation mechanism (Fig. 1a–g). We must consider the possibility that the decreasing number of Gems results from the decreasing number of large motor neurons in ALS, because the number of Gems is positively correlated with the size of the cell.[39, 40] Moreover, large motor neurons are more vulnerable to ALS than small ones.[41] To rule out this possibility, multiple regression analysis should be conducted to investigate whether ALS is an independent factor determining the number of Gems regardless of cell size. If our hypothesis is correct, the next question is whether the decreasing number of Gems results from a direct or indirect function of TDP-43. The number of Gems also declines due to decreasing transcriptional activity.

The susceptibility of CD8+ T cells to ‘domination’ was a direct correlate of higher kinetic stability of the competing CD8+ T-cell cognate ligand. When high affinity competitive CD8+ T cells were deleted by self-antigen expression, competition was abrogated. These findings show, for the first time to our knowledge, the existence of regulatory mechanisms

RG7420 that direct the responding CD8+ T-cell repertoire toward epitopes with high-stability interactions with MHC class I molecules. They also provide an insight into factors that facilitate CD8+ T-cell coexistence, with important implications for vaccine design and delivery. “
“Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown aetiology. Interleukin (IL)-1β plays an important PLK inhibitor role in inflammation and has been associated with fibrotic remodelling. We investigated the balance between IL-1β and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) and serum as well as the influence of genetic variability in the IL1B and IL1RN gene on disease susceptibility and cytokine levels. In 77 IPF

patients and 349 healthy controls, single nucleotide polymorphisms (SNPs) in the IL1RN and IL1B genes were determined. Serum and BALF IL-1Ra and IL-1β levels were measured using a multiplex suspension bead array system and were correlated with genotypes. Both in serum and BALF a significantly decreased IL-1Ra/IL-1β ratio was found in IPF patients compared to healthy controls. In the IL1RN gene, one SNP was associated with both the susceptibility to IPF and reduced IL-1Ra/IL-1β ratios in BALF. Our results

show that genetic variability in the IL1RN gene may play a role in the pathogenesis of IPF and that this Megestrol Acetate role may be more important than thought until recently. The imbalance between IL-1Ra and IL-1β might contribute to a proinflammatory and pro-fibrotic environment in their lungs. Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown aetiology, and is characterized by an extremely poor prognosis of 2–4 years after diagnosis [1–3]. The pathogenetic mechanisms underlying IPF are incompletely understood. The disease is characterized by abnormal repair and airway remodelling and is associated with increased proinflammatory and pro-fibrotic signals. Previous research has shown that interleukin (IL)-1 cytokines are involved in the development of fibrosis [4]. The IL-1 family consists of three structurally related proteins, of which two are agonists (IL-1α and IL-1β) and the third, IL receptor antagonist (IL-1Ra), is a competitive antagonist. IL-1Ra is the inhibitor of these IL-1 agonists and acts by competitively binding to IL-1 receptors without eliciting signal transduction [5].

To test this hypothesis, we characterized a large (1739 subjects) number of multi-ethnic patients with

breast cancer (which over-expresses cyclin B1) and matched controls for anti-cyclin B1 immunoglobulin (Ig)G antibodies. Multivariate analyses, after adjusting for the covariates, showed that cancer-free individuals had significantly higher levels of naturally occurring IgG antibodies to cyclin B1 than patients with breast cancer (mean ± standard deviation: 148·0 ± 73·6 BMS-777607 solubility dmso versus 126·1 ± 67·8 arbitrary units per ml; P < 0·0001). These findings may have important implications for cyclin B1-based immunotherapy against breast cancer and many other cyclin B1-over-expressing malignancies. "
“Up-regulation of interleukin (IL)-17 in small intestinal mucosa has been reported in coeliac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL-17 immunity in different stages of CD, including transglutaminase antibody (TGA)-positive children with potential CD, children with untreated and gluten-free diet-treated CD and in children with T1D. Immunohistochemistry was used for identification of IL-17 and forkhead box protein 3 (FoxP3)-positive

cells and quantitative polymerase chain reaction (qPCR) for IL-17, FoxP3, retinoic acid-related orphan receptor (ROR)c and interferon

(IFN)-γ transcripts. IL-1β, IL-6 and IL-17 were studied in supernatants from biopsy cultures. Expression of the apoptotic see more markers BAX and bcl-2 was evaluated in IL-17-stimulated CaCo-2 cells. The mucosal expression of IL-17 and FoxP3 transcripts were elevated in individuals with untreated CD when compared with the TGA-negative reference children, children with heptaminol potential CD or gluten-free diet-treated children with CD (P < 0·005 for all IL-17 comparisons and P < 0·01 for all FoxP3 comparisons). The numbers of IL-17-positive cells were higher in lamina propria in children with CD than in children with T1D (P < 0·05). In biopsy specimens from patients with untreated CD, enhanced spontaneous secretion of IL-1β, IL-6 and IL-17 was seen. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17 could, however, serve as a biomarker for the development of villous atrophy and active CD. Coeliac disease (CD) and type 1 diabetes (T1D) are immune-mediated diseases sharing a predisposing genetic background: human leucocyte antigen (HLA)-DQ2 and HLA-DQ8. In both CD and T1D intestinal inflammation has been observed as altered mucosal cytokine expression and increased activation of intestinal T lymphocytes [1–3].

parvum infection (17,32). Recently cloned from C. parvum, P2 is one of the three acidic ribosomal proteins, including P0 and P1. These P proteins are potential vaccine targets owing to their expected surface localization and immunogenicity (19,24). The P2 antigen specifically is reactive with ∼70% of sera from adults in highly endemic countries. Strong anti-P2 antibody responses were observed in serum samples from Cryptosporidium-infected Haitian individuals that were also antibody positive for the Cp23 antigen (19). A strong and persistent cell-mediated PS-341 in vivo response is important in response and resistance to Cryptosporidium and depends,

in part, on the initial encounter between the parasite/parasitic antigens and antigen-presenting cells such as DCs. Therefore, the ability of parasite antigen to induce dendritic cells should correlate with a strong cellular response. Previously, it has been reported that Cp23 and Cp40 recombinant antigens induce a strong cellular T-cell response in mice and humans (33–35). Hence, these antigens should stimulate

DCs to produce significant levels of IL-12p70. Recombinant Cp17 did not stimulate significant cellular immune response in one study in mice (34) but Selleck Crizotinib does elicit strong antibody responses, whereas the P2 antigen induces moderate levels of cellular immune responses (24). That recombinant Cp17 and P2 antigens induce modest cellular immune responses may be reflected by the ability of these antigens to activate mouse DC to produce IL-12p70 or that native antigen is necessary to induce a more optimal dendritic cell response. One human sample in the present study demonstrated significant IL-12p70 expression in response to P2, and no significant response was observed to Cp17. As noted, solubilized antigens stimulated

large amounts of IL-12p70 expression compared to excysted sporozoites in mouse BMDCs. Differences in spatial configuration, glycosylation, Adenosine triphosphate DNA content or concentrations needed for induction may have contributed to observed differences in response. Barakat et al. (10) showed that IFN-α/β expression was detectable at sporozoite-to-DC exposure ratios higher than tested in our trials. The downstream pathway involved in the induction of immune effects by parasite proteins in the DCs appears, in part, to be mediated through TLR signalling, via the adaptor protein MyD88. However, it is unclear which specific TLR binds to the peptides, possibly by activating NF-kB signalling cascade (36). In murine toxoplasmosis, splenic DCs from MyD88−/− mice display severely impaired T. gondii-induced IL-12 responses, which, in turn, was required for promoting IFN-γ production by NK cells and subsequent activation of inflammatory monocytes and macrophages to allow them to kill the parasites (37). This is reflected in a marked reduction in serum IL-12 levels in infected MyD88 knockout animals (38).

The vaccines were expensive to make, and despite time controlled reactions, the site of linkage of the carrier to hCGβ or HSD, had inevitable variations. We decided therefore to make a recombinant ZD1839 mw vaccine in which hCGβ gene was fused at the C-terminal end with

B subunit of Escherichia coli heat labile enterotoxin (LTB) (Fig. 6). The choice of LTB as carrier was based on the consideration that it is free of regions causing immune suppression. It is a good mucosal adjuvant75 and generates both IgG and IgA antibody response.76 The complex hCGβ-LTB was cloned and expressed in yeast Pichia pastoris as a secretory protein. The conjugate was purified using Selleck Pexidartinib ammonium sulfate fractionation followed by ion-exchange chromatography.72 It was absorbed on alhydrogel for immunization. MIP at 5 × 107 autoclaved bacilli was injected as adjuvant intramuscularly. Three primary injections of hCGβ-LTB along with MIP at fortnightly interval generated in every Balb/c mouse bioeffective anti-hCG antibodies. On day 37, the titers were already several fold higher than 50 ng/mL in every mouse. A booster around the 4th month enhanced further the titers to well over 100-folds higher than the protective threshold of 50 ng/mL. The immune response was reversible with antibodies declining with time, but was still well above 50 ng/mL after

8 months. Immunogenicity of the recombinant vaccine was also observed in inbred mice of different genetic background,

Protein tyrosine phosphatase encompassing haplotypes H-2d, H-2k, H-2b, H-2s, and H-2q. This vaccine has received the approval of the Indian National Review Committee on Genetic Manipulation. It is being produced under GMP conditions for pre-clinical toxicology. If found safe, it is planned to conduct clinical trials with this vaccine for preventing pregnancy, as well as for its possible therapeutic action on cancers expressing hCG or its subunits. Besides the three vaccines described earlier, namely hCGβ-TT,77 hCGβ carboxy terminal peptide (CTP)-DT70, and HSD-TT,4,62 which went up to the stage of phase I safety and/or phase II efficacy clinical trials for fertility control, the following are the other vaccines devised against hCG, which are primarily being tested against cancers expressing hCG. In view of the carrier-induced immune suppression brought by the hCGβ vaccine linked to TT as carrier, the carrier was replaced by T non-B peptides peptides, which could communicate across various MHC haplotypes, but not have disadvantage of TT. Gupta et al.78 conjugated hCGβ to three promiscuous Th peptides from the measles virus fusion protein, influenza virus hemagglutinin, and HIV-1 reverse transcriptase. Conjugates were adsorbed on alum and studied for their immunogenicity in mice of different haplotypes.

Other Articles published in this series Paraneoplastic neurological syndromes. Clinical and Experimental Immunology 2014, 175: 336–48.

Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies. Clinical and Experimental Immunology 2014, 175: 359–72. Monoclonal antibodies in treatment of multiple sclerosis. Clinical and Experimental Immunology 2014, 175: 373–84. CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum Selleckchem Torin 1 of inflammatory central nervous system disorders. Clinical and Experimental Immunology 2014, 175: 385–96. Requirement for safety monitoring for approved multiple sclerosis therapies: an overview. Clinical and Experimental Immunology 2014, 175: 397–407. Myasthenia gravis: an update for the clinician. Clinical and Experimental Immunology 2014, 175: 408–18. Cerebral vasculitis in adults: what are the steps in order to establish the diagnosis? Red flags and pitfalls. Clinical and Experimental Immunology 2014, 175: 419–24. Multiple sclerosis treatment and infectious issues: update 2013.

Clinical and Experimental Immunology 2014, 175: 425–38. Diagnosis, pathogenesis and treatment of myositis: recent advances 2014, 175: 349–58. Management of disease-modifying treatments in neurological autoimmune diseases of the central nervous system 2014, 176: 135–48. Neuromyelitis GDC-0199 clinical trial optica (NMO, Devic’s syndrome) is an inflammatory disorder of the central nervous system (CNS) that presents typically with relapses of optic neuritis (ON) or myelitis [1-4]. In recent years, the condition has raised enormous interest among scientists and clinical neurologists, fuelled by the detection of a highly specific serum immunoglobulin (Ig)G autoantibody Celecoxib (NMO-IgG) targeting the most abundant astrocytic water channel aquaporin-4 (AQP4) [5-8]. NMO-IgG/AQP4-antibodies are

present in up to 80% of patients with NMO [8-11]. This seminal discovery has – together with previous neuropathological work that had already suggested humoral mechanisms to be relevant in the disease pathogenesis [12] – made clear that in most cases NMO is not a subform of multiple sclerosis (MS), as had been assumed for decades, but rather an autoimmune condition with an immunopathogenesis distinct from that of MS despite considerable overlap in clinical presentation and paraclinical findings. AQP4-antibody-positive NMO is part of an expanding spectrum of humorally mediated autoimmune diseases of the CNS that have been identified over the last few years [13, 14]. Several studies suggest that optimum treatment options may differ between NMO and MS, which underscores the necessity for a timely and accurate diagnosis.

During the course of a malaria infection, a wide array of immune effectors are activated. The first acute phase stimulates an inflammatory response with the release of cytotoxic compounds followed by acquired response and antibody production. Previous exposure to the pathogen confers a partial protection to a subsequent infection, a phenomenon coined ‘premunition’ by very early work on avian malaria [51]. Cellier Holzem et al. [52] infected immunologically naive domestic canaries with Plasmodium relictum. Thirty-four days after this primary

infection, when the birds had recovered their initial haematocrit and body mass values, surviving canaries were re-infected with the homologous strain. In agreement with the idea of premunition, re-exposed birds were better able to cope with the infection, keeping parasitaemia at lower levels and managing to maintain constant haematocrit

selleck screening library and body mass. Primary infected canaries produced more haptoglobin, a protein of the acute-phase response, compared with noninfected birds. However, haptoglobin did not differ between primary and secondary infected birds, suggesting that while inflammatory effectors are involved in the control of the initial acute phase of the infection, long-lasting partial immunity relies on memory effectors. Pioneering work conducted on buy Vorinostat rodent malaria has stressed the importance of host immunity as a component of malaria virulence. Pro-inflammatory cytokines are important immune effectors involved in malaria resistance. Up-regulation of pro-inflammatory cytokines is often associated with a resistance phenotype

prone to immunopathology damage. On the contrary, up-regulation of anti-inflammatory cytokines confers a susceptible phenotype to microparasites and a protection towards immunopathology. Long et al. [53, 54] used phenotypic manipulations of both pro- and anti-inflammatory cytokines in mice infected Etoposide ic50 with Plasmodium chabaudi. They found that blockade of IL-10 (an anti-inflammatory cytokine) reduced parasitaemia but, nevertheless, exacerbated malaria virulence (i.e. mouse mortality) [53]. Similarly, blocking the TNF-α receptors induced an increase in parasite density while reducing disease severity [54]. Overall, there is strong evidence based on human and rodent studies that malaria virulence has an immune-based component [55, 56]. Building on this previous work, Bichet et al. [57] experimentally infected domestic canaries whose inducible nitric oxide synthase (iNOS) activity was inhibited by a drug (aminoguanidine). Inducible nitric oxide synthase catalyses the production of nitric oxide (NO), a nitrogen reactive species with cytostatic and cytotoxic effect on different Plasmodium species both in vitro and in vivo [58].