Interleukin 10 Production Correlates with Pathology in Human Leishmania Donovani Infections

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1993 Jul 1

PMID 8326000

Citations 149

Authors

H W Ghalib

M R Piuvezam

Y A Skeiky

M Siddig

F A Hashim

A M El-Hassan

D M Russo

S G Reed

Affiliations

Soon will be listed here.

Abstract

We have found that an important Th2 cytokine, IL-10, is produced by tissues from patients acutely infected with Leishmania donovani. In all individuals tested, IL-10 mRNA production was increased in lymph nodes taken during acute disease over that observed in postacute samples. In contrast, both pre- and posttreatment lymph nodes had readily detected mRNA for IFN-gamma and IL-2. A down-regulating effect of IL-10 on leishmania-induced proliferative responses was demonstrated when Hu rIL-10 was added to cultures of PBMC from clinically cured individuals. PBMC from individuals with acute visceral leishmaniasis responded to stimulation with leishmania lysate by producing IL-10 mRNA. Simultaneously cultured PBMC collected from the same patients after successful chemotherapy produced no detectable IL-10 mRNA after leishmania antigen stimulation. Neutralizing anti-IL-10 mAb added to PBMC from patients with acute visceral leishmaniasis markedly increased the proliferative response to leishmania lysate. Finally, we observed mRNA for IL-10 and IFN-gamma concurrently in a lesion from a patient with post-kala-azar dermal leishmaniasis (PKDL). These results indicate the production of IL-10 during L. donovani infection, and suggest a role for this cytokine in the regulation of immune responsiveness during visceral leishmaniasis.

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References

MANSON-BAHR P, HEISCH R, Garnham P . Studies in leishmanifasis in East Africa. IV. The Montenegro test in kala-azar in Kenya. Trans R Soc Trop Med Hyg. 1959; 53:380-3. DOI: 10.1016/0035-9203(59)90038-0. View

Carvalho E, Badaro R, Reed S, Jones T, Johnson Jr W . Absence of gamma interferon and interleukin 2 production during active visceral leishmaniasis. J Clin Invest. 1985; 76(6):2066-9. PMC: 424308. DOI: 10.1172/JCI112209. View

Reed S, Badaro R, Masur H, Carvalho E, Lorenco R, LISBOA A . Selection of a skin test antigen for American visceral leishmaniasis. Am J Trop Med Hyg. 1986; 35(1):79-85. DOI: 10.4269/ajtmh.1986.35.79. View

Wyler D . Circulating factor from a kala-azar patient suppresses in vitro antileishmanial T cell proliferation. Trans R Soc Trop Med Hyg. 1982; 76(3):304-6. DOI: 10.1016/0035-9203(82)90174-2. View

Murray H, Rubin B, Rothermel C . Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine. J Clin Invest. 1983; 72(4):1506-10. PMC: 370435. DOI: 10.1172/JCI111107. View

Reed S, Barral-Netto M, Inverso J . Treatment of experimental visceral leishmaniasis with lymphokine encapsulated in liposomes. J Immunol. 1984; 132(6):3116-9. View

Feinberg A, Vogelstein B . "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984; 137(1):266-7. DOI: 10.1016/0003-2697(84)90381-6. View

Mosmann T, Cherwinski H, Bond M, Giedlin M, Coffman R . Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986; 136(7):2348-57. View

Barral A, Carvalho E, Badaro R, Barral-Netto M . Suppression of lymphocyte proliferative responses by sera from patients with American visceral leishmaniasis. Am J Trop Med Hyg. 1986; 35(4):735-42. DOI: 10.4269/ajtmh.1986.35.735. View

10.

Sacks D, Lal S, Shrivastava S, Blackwell J, NEVA F . An analysis of T cell responsiveness in Indian kala-azar. J Immunol. 1987; 138(3):908-13. View

11.

Murray H, Stern J, Welte K, Rubin B, Carriero S, Nathan C . Experimental visceral leishmaniasis: production of interleukin 2 and interferon-gamma, tissue immune reaction, and response to treatment with interleukin 2 and interferon-gamma. J Immunol. 1987; 138(7):2290-7. View

12.

Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-9. DOI: 10.1006/abio.1987.9999. View

13.

Cherwinski H, Schumacher J, Brown K, Mosmann T . Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987; 166(5):1229-44. PMC: 2189643. DOI: 10.1084/jem.166.5.1229. View

14.

Reed S . In vivo administration of recombinant IFN-gamma induces macrophage activation, and prevents acute disease, immune suppression, and death in experimental Trypanosoma cruzi infections. J Immunol. 1988; 140(12):4342-7. View

15.

Lewis D, Prickett K, Larsen A, Grabstein K, Weaver M, Wilson C . Restricted production of interleukin 4 by activated human T cells. Proc Natl Acad Sci U S A. 1988; 85(24):9743-7. PMC: 282856. DOI: 10.1073/pnas.85.24.9743. View

16.

Heinzel F, Sadick M, Holaday B, Coffman R, Locksley R . Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989; 169(1):59-72. PMC: 2189187. DOI: 10.1084/jem.169.1.59. View

17.

Fiorentino D, Bond M, Mosmann T . Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989; 170(6):2081-95. PMC: 2189521. DOI: 10.1084/jem.170.6.2081. View

18.

Moore K, Vieira P, Fiorentino D, Trounstine M, Khan T, Mosmann T . Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990; 248(4960):1230-4. DOI: 10.1126/science.2161559. View

19.

Zwingenberger K, Harms G, Pedrosa C, Omena S, Sandkamp B, Neifer S . Determinants of the immune response in visceral leishmaniasis: evidence for predominance of endogenous interleukin 4 over interferon-gamma production. Clin Immunol Immunopathol. 1990; 57(2):242-9. DOI: 10.1016/0090-1229(90)90038-r. View

20.

Ehlers S, Smith K . Differentiation of T cell lymphokine gene expression: the in vitro acquisition of T cell memory. J Exp Med. 1991; 173(1):25-36. PMC: 2118764. DOI: 10.1084/jem.173.1.25. View