IngentaConnect IL-15 in human visceral leishmaniasis caused by Leishmania infant...

Authors: MILANO, S.¹; BELLA, G. DI¹; D'AGOSTINO, P.²; BARBERA, C.¹; CARUSO, R.¹; ROSA, M. LA¹; FERLAZZO, V.¹; VITALE, G.³; RUSSA, C. LA³; GAMBINO, G.³; CHIFARI, N.³; MANSUETO, S.³; CILLARI, E.⁴

Source: Clinical & Experimental Immunology, Volume 127, Number 2, February 2002 , pp. 360-365(6)

Publisher: Blackwell Publishing

Abstract:

SUMMARY

Interleukin (IL)-15 is a recently discovered cytokine with the ability to stimulate the proliferation activity of Th1 and/or Th2 lymphocytes. Here, we investigated the involvement of IL-15 in the immune response to Leishmania infantum infection by studying patients with visceral leishmaniasis (VL). We found that IL-15 is produced by leishmanial antigen (LAg)-stimulated peripheral blood mononuclear cells (PBMC) from active VL patients at a significantly higher level than those produced by cells from healed VL subjects or healthy controls. A significant increase in IL-15 serum blood levels was also observed in acute VL patients compared with healed ones. Furthermore, recombinant IL-15 had an appreciable effect in vitro in reducing IL-4 and increasing the production of IL-12 in response to LAg, but it was ineffective in altering the production of interferon-γ (IFN-γ). The production of endogenous IL-15 in acute VL patients appeared to be insufficient to activate both IFN-γ and IL-12, as attested by the absence of modification of these two cytokines by neutralization experiments in the presence of anti-IL-15 monoclonal antibodies (MoAB). On the contrary, the neutralization of IL-15 increased IL-4 production. Together, these results indicate that endogenous IL-15 plays a role in the suppression of Th2-type cytokines, even though it does not enhance the production of Th1 cytokines in acute VL patients. Since IL-15, in the presence of anti-IL-4 MoAb, caused a further increase in IL-12 production and led to a significant production of IFN-γ, one of its indirect effects on Th1 cell activation could be due to the latter's effect on Th2 cytokines such as IL-4. Therefore, our observations indicate that there is a potential for IL-15 to augment the T-cell response to human intracellular pathogens.

Keywords: IL-15; IL-4; IL-12; IFN-γ; leishmaniasis

Document Type: Research article

DOI: 10.1046/j.1365-2249.2002.01749.x

Affiliations: 1: Department of Biopathology and Biomedical Methodologies, University of Palermo, 2: Department of Immuno-Hematology and Transfusion, University of Palermo and 3: Institute of Internal and Geriatric Medicine, Faculty of Medicine, University of Palermo, 4: Cervello Hospital, Clinical Pathology and Microbiology Laboratories, Palermo, Italy

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IL-15 in human visceral leishmaniasis caused by Leishmania infantum