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* Unit of Clinical Immunology, Uppsala University, Uppsala, Sweden;
Department of Clinical Pathology and Microbiology, Alribate University Hospital, Khartoum, Sudan;
Department of Microbiology and Immunology, University of Khartoum, Sudan; and
King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
Infection with Leishmania donovani is associated with IL-10 as well as with GM-CSF. Immune complexes (IC) exert important functions by stimulation of monocytes/macrophage-mediated production of pro- and anti-inflammatory cytokines in rheumatic diseases. In this investigation, we have explored IC-induced cytokine production during Leishmania infection. Sera from 43 patients with visceral leishmaniasis (VL), 17 patients with post-kala-azar dermal leishmaniasis, and 20 healthy Sudanese controls were precipitated with polyethylene glycol (PEG). The PEG precipitates were added to serum-free PBMC for 20 h,whereupon supernatant levels of IL-1
, IL-6, IL-10, IL-1 receptor antagonist protein, TNF-
, TNF receptor p75, and GM-CSF were investigated using ELISA. Circulating levels of C1q-binding IC were also measured in the serum samples. PEG precipitates from Leishmania-infected patients induced significantly higher levels of GM-CSF (p = 0.0037) and IL-10 (p < 0.0001), as well as of IL-6 (p < 0.0001) and IL-1 receptor antagonist (p = 0.0238) as compared with PEG precipitates from controls. Patients with acute VL as well as VL patients receiving sodium stibogluconate treatment displayed significantly increased levels of PEG precipitate-induced GM-CSF. The induction of GM-CSF by circulating IC was especially prominent in acute VL patients receiving sodium stibogluconate treatment; ANOVA revealed significant interaction between disease activity and treatment for PEG precipitate-induced levels of GM-CSF (disease activity, p = 0.0006; treatment, p = 0.0005; interaction, p = 0.0046). Parallel associations were determined for C1q-binding immune complexes, but not for any cytokine other than GM-CSF. The importance of IC-induced GM-CSF in leishmaniasis warrants further study.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This investigation was supported by grants from the Swedish Society of Medicine, King Gustav V’s 80-years Fund, Swedish League against Rheumatism, Ugglas Foundation, Groschinsky Foundation, Viberg Foundation, and Swedish Fund for Research Without Animal Experiments.
2 A.I.E. and E.A. contributed equally.
3 Address correspondence and reprint requests to Dr. Johan Rönnelid, Unit of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University, SE-75185 Uppsala, Sweden. E-mail address: johan.ronnelid{at}klinimm.uu.se
4 Abbreviations used in this paper: VL, visceral leishmaniasis; CIC, circulating immune complex; HSA, human serum albumin; IC immune complex; IL-1ra, IL-1 receptor antagonist protein; PEG, polyethylene glycol; PKDL, post-kala-azar dermal leishmaniasis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TNF-Rp75, TNF receptor p75.
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