Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria

Abstract

SUMMARYPlasma samples from children with mild and severe Plasmodium falciparum malaria and from children with unrelated diseases were collected to investigate whether the elinieal outcome of infection was associated with plasma factors whieh reflected the activity of different cells of the immune system. Children with severe P.fahiparum malaria had significantly higher plasma levels o( soluble IL-2R than children with mild malaria. Plasma levels of 1L-2R and levels of parasitaemia were significantly correlated. Neither parasitaemla nor plasma levels of tumour necrosis factor-alpha {TNF-a). IL-6. lymphotoxin (LT). interferon-gamma (IFN-y). IL-4, soluble IL-4R or soluble CDS differed significantly between the two groups of children with niakiria. High plasma levels of soluble CDS were associated with failure oflymphocytes to produce IFN-//>j [•//»•<» following stimulation with P. falciparum antigen. We conelude that soluble IL-2R is a useful marker of disease severity independently of the association wiih levels of parasitaemia, and that functional regulation of different lymphocyte subsets oeeurs during acute malaria episodes.

Identification of Inflammatory Biomarkers for Pediatric Malarial Anemia Severity Using Novel Statistical Methods

“…Eosinophils are known to produce granule proteins (e.g., eosinophil cationic protein [ECP]) whose levels are correlated with TNF-␣ and IL-2R during malarial infections (25). Findings presented here showing that soluble IL-2R levels are significant negative predictors of Hb levels are consistent with previous studies showing that elevated IL-2R is associated with enhanced malaria disease severity (18). The potential effect of the IL-13/eotaxin pathway on erythropoiesis and the influence of IL-2R in regulating this process are largely unexplored.…”

“…Based on findings presented here and placed into the context of previous studies, we propose a model in which IL-12 and IFN-␥ are two of the primary cytokines responsible for promoting successful erythropoiesis in children with malaria (31,32), while high levels of IL-2R may serve to dampen excessive type 1 immunity (18). The model further proposes that eotaxin may recruit eosinophils to the deeper tissues (including bone marrow), where they and other cell types may produce IL-13 to dampen the inflammatory responses (30), but in the process, direct effects of protein granules (or other local toxic mediators) may contribute to the suppression of erythropoiesis.…”

IL-2 Contributes to Maintaining a Balance between CD4+Foxp3+ Regulatory T Cells and Effector CD4+ T Cells Required for Immune Control of Blood-Stage Malaria Infection

“…We therefore questioned whether decreased IL-2 secretion by effector CD4 + T cells might explain our findings of significantly lower proliferation of Treg cells compared with effector CD4 + T cells and decreased numbers of CD4 + Foxp3 + T cells in WT mice during P. chabaudi AS infection. Earlier studies demonstrated that IL-2 levels are decreased in Plasmodium-infected individuals (41)(42)(43). The notion that IL-2 might be important in regulating the balance between effector Th1 cells and natural Treg cells during malaria has been suggested, but the exact role of this cytokine remains unknown (6,7,25,44).…”

Interferon-γ—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria

“…Whereas several case-control studies found higher plasma IFN-␥ levels in SM compared with UM patients [122][123][124][125][126], various similar studies have found higher plasma levels of TNF-␣ [120,[127][128][129][130], IL-2R [131], IL-6 [127,132], IL-1␣ [128], or IL-1␤ [130] but never IFN-␥ in SM compared with UM patients. Furthermore, plasma levels of IL-12 [130,[133][134][135][136] and IL-18 [134 -136], which induce IFN-␥, have been found to be lower in SM than UM patients.…”