Variation of Cytokine Patterns Related to Therapeutic Response in Diffuse Cutaneous Leishmaniasis

Abstract

Diffuse cutaneous leishmaniasis is a rare entity characterized by disseminated cutaneous nodules associated with specific anergy to leishmanial antigens. A low but not absent IFN-gamma expression by cells present in cutaneous lesions has been documented during the active phase of diffuse cutaneous leishmaniasis. In this study we confirm this observation, and extend it by showing a similar pattern in peripheral blood mononuclear cells and the variation of mRNA cytokine expression pattern during different stages of the disease. During active disease, patients did not express mRNA for IFN-gamma, while expressing mRNA for IL-2, IL-4, and IL-10. In contrast, an expression of IFN-gamma and low IL-10 was observed after treatment-induced transient healing of cutaneous lesions. In three patients we have been able to analyze a third PBMC sample obtained after clinical relapse, documenting in all of them decreased IFN-gamma expression with no expression of IL-10. Although there was an association between the appearance of IFN-gamma expression and clinical improvement, with marked expression of IFN-gamma mRNA and decreased expression of mRNA for IL-10 after treatment, this was not sufficient to prevent relapse in these patients. Therefore, it is possible that factors other than the cytokines characteristic of the Th1 and Th2 balance are implicated in the inability of diffuse cutaneous leishmaniasis patients to mount an anti-Leishmania immune response causing clinical improvement.

Therapy of Venezuelan patients with severe mucocutaneous or early lesions of diffuse cutaneous leishmaniasis with a vaccine containing pasteurized Leishmania promastigotes and bacillus Calmette-Guerin: preliminary report

“…observed apparent parasitological cures after treatment of two DCL patients with pentamidine, allopurinol and IFN-gamma, but relapse began three months after suspending treatment, in spite of the re-establishment of conditions favoring a Th1 response . Transitory clinical improvement induced by treatment has been associated with expression of IFN-gamma mRNA, but relapse was not prevented (Bomfim et al 1996).…”

Treatment of two patients with diffuse cutaneous leishmaniasis caused by Leishmania mexicana modifies the immunohistological profile but not the disease outcome

“…Patients with diffuse cutaneous leishmaniasis have a reduced IFN-␥ expression by cells in cutaneous lesions as well as in peripheral blood mononuclear cells (Bomfim et al 1996). In granulomas of DCL patients, a preponderance of Th-2 cytokines is present, whereas in LCL patients a Th-1 cytokine pattern with production of IFN-␥ predominates (Tapia et al 1993).…”

Early Enhanced Th1 Response afterLeishmania amazonensisInfection of C57BL/6 Interleukin-10-Deficient Mice Does Not Lead to Resolution of Infection

“…This cytokine has been shown to play a role in limiting IFN-␥ production in T cells via downregulation of IL-12 production in both macrophages and dendritic cells and in downregulating antigen-presenting cell function by decreasing the expression of major histocompatibility complex class II and regulating the responsiveness and/or expression of costimulatory molecules in the antigen-presenting cell population (10, 13, 14-16, 26, 29, 36). In addition, IL-10 has been associated with decreased immune responses to cutaneous leishmaniasis in people (6,40), and inhibition of IL-10 during the recall response increases IFN-␥ levels (40). However, anti-IL-10 treatment did not alter the course of infection in L. major-susceptible BALB/c mice or L. major-resistant C57BL/6 mice (8).…”