Potential role for interleukin-10 in the immunosuppression associated with kala azar.

Abstract

Patients with acute kala azar are generally nonreactive in a number of immunologic assays, including T cell proliferation and generation of macrophage-activating cytokines, principally IFN-'y, in response to leishmania antigens in vitro. To test for potential immunosuppressive factors, a series of T cell lines and clones were established from patients with acute kala azar, from patients after chemotherapy for kala azar, and from skin test-positive adults from the same endemic region. Although CD4+ T cell lines and clones could be readily established from the skin test-positive adults, lines and clones from acute or treated patients were heavily biased in expression of CD8+. The CD8 + cells from acute patients did not themselves release cytokines in response to leishmania antigens in vitro, but markedly affected the cytokine profile of peripheral blood mononuclear cells isolated 1 yr later after recovery. Addition of the CD8 + cells caused inhibition of lymphoproliferation and IFN-y release, with augmentation of IL-6 and IL-10 release. The inhibitory effects of the CD8+ cells could be partially abrogated by antibodies to IL-10 but not by antibodies to IL4. Analysis of four patients with acute kala azar demonstrated release of IL-10 that could not be demonstrated in supernatants from asymptomatic skin test-positive individuals. Generation of IL-10 may contribute to the profound suppression of IFN--y release that occurs during kala azar due to Leishmania chagasi. (J. Clin. Invest. 1993. 92:2626-2632.) Key words: leishmania -interleukin-10 * kala azar * interferon-'y -immunosuppression

Anti-leishmanial IgE antibodies: a marker of active disease in visceral leishmaniasis.

“…[16][17][18][19]36 Documentation of high levels of specific IgE indicates that this immunoglobulin class is a marker of Th2 activation in VL.…”

“…While lymphocytes from subjects who are able to control their L. chagasi infections produce interferon-␥ (IFN-␥) upon stimulation with leishmanial antigen in vitro, 13 the immunologic response in patients with VL is characterized by an absence of interleukin-2 (IL-2) and IFN-␥ production, 14,15 and a high level of IL-10 mRNA expression and IL-10 production. [16][17][18][19] Although dissemination of leishmanial infection in mice is dependent on IL-4, 20 evidence for IL-4 production in human VL is minimal or absent. 19,21 Since IL-4 is the primary cytokine that induces T helper cell type 2 (Th2) activation and B cell differentiation leading to IgE synthesis, 22,23 we measured levels of total IgE and specific antiLeishmania IgE antibodies in individuals with different clinical forms of VL and determined whether these levels were associated with disease severity, levels of IgG antibodies, and response to therapy.…”

Cytokine profile and pathology in human leishmaniasis

“…These observations clearly indicate that absence or poor IFN-γ production is a marker of susceptibility to visceral leishmaniasis. Although it is likely that several mechanisms may participate in the inability of lymphocytes from visceral leishmaniasis patients to produce this cytokine, one important point is related to the imbalance of cytokines produced in response to Leishmania antigens, i.e., high production of IL-4 and IL-10 and low IL-2 and IFN-γ production (14)(15)(16)(17)(18). Although lymphocytes from patients with visceral leishmaniasis have a strong expression of mRNA for IL-4 (16,18) and sera from visceral leishmaniasis patients have high IL-4 levels (14), there is no evidence that IL-4 is involved in the downregulation of the Th1 type of response in human leishmaniasis.…”

In vitro production of type 1 and type 2 cytokines by peripheral blood mononuclear cells from subjects coinfected with human immunodeficiency virus and Leishmania infantum.

“…This may facilitate the intracellular survival of the parasite and influence the unfavorable outcome of the disease. 4,5 As far as HIV is concerned, recent in vitro experiments have reported a dominant type 1 cytokine profile as being more protective than a dominant type 2 cytokine profile. 6 A shift from a Th1 to a Th2 cytokine pattern has been previously hypothesized to parallel or even precede the progressive CD4ϩ impairment that accompanies the transition towards the final stage of acquired immunodeficiency syndrome (AIDS).…”