title: Circulating immune complexes (IC) and IC-induced levels of GM-CSF are increased in sudanese patients with acute visceral Leishmania donovani infection undergoing sodium stibogluconate treatment: implications for disease pathogenesis.
abstract: 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-1beta, IL-6, IL-10, IL-1 receptor antagonist protein, TNF-alpha, 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.
authors.affiliation: Unit of Clinical Immunology, Uppsala University, Uppsala, Sweden.
authors.forename: Amir Ibrahim
authors.initials: AI
authors.lastname: Elshafie
authors.forename: Erik
authors.initials: E
authors.lastname: Ahlin
authors.forename: Linda
authors.initials: L
authors.lastname: Mathsson
authors.forename: Gehad
authors.initials: G
authors.lastname: ElGhazali
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood*; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D017452:Receptors, IgG / Q000502:physiology
chemical_list: D000936:Antigen-Antibody Complex; D000981:Antiprotozoal Agents; D016207:Cytokines; D017452:Receptors, IgG; D011092:Polyethylene Glycols; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000967:Antimony Sodium Gluconate