Profiles of IFN-gamma and Its Regulatory Cytokines (IL-12, IL-18 and IL-10) in Peripheral Blood Mononuclear Cells from Patients with Multidrug-resistant Tuberculosis

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2002 Jun 18

PMID 12067307

Citations 20

Authors

J-S Lee

C-H Song

C-H Kim

S-j Kong

M-H Shon

H-J Kim

J-K Park

T-H Paik

E-K Jo

Affiliations

Soon will be listed here.

Abstract

This study investigated the profiles of IFN-gamma and its regulatory cytokines (IL-12, IL-18 and IL-10) in response to a purified protein derivative (PPD) antigen in peripheral blood mononuclear cells (PBMC) from 18 HIV-negative patients with multidrug-resistant tuberculosis (MDRTB), and compared them with those from 19 healthy tuberculin reactors (HTR). ELISA results showed that following stimulation with PPD, IFN-gamma production was significantly reduced, whereas production of both IL-18 and IL-10 was significantly elevated in MDRTB patients compared with HTR. Three out of 18 patients with MDRTB of greater than 4 years duration showed significantly elevated IL-12 p70 production, induced by in vitro PPD stimulation of their PBMC, when compared with data from HTR. However, when taken as a group, MDRTB patients were similar to HTR in their IL-12 p70-producing capacity. IL-12 p70 protein paralleled IL-12 p40 protein expression. In addition, the production of IL-12 p40 was significantly correlated with IL-10 in all patients, but was not correlated with IFN-gamma. Neutralization of IL-10 increased IL-12 p40 about twofold, but did not significantly alter IFN-gamma induction in MDRTB. IFN-gamma in MDRTB was highly correlated with lymphoproliferation and CD4 counts, but was not correlated with IL-12, IL-18 or IL-10 production. Our findings suggest that patients with MDRTB have dysregulated IL-12, IL-18 and IL-10 production during Mycobacterium tuberculosis infection, and the cytokine profiles are similar to those in patients with drug-sensitive advanced TB previously reported in the literature. In addition, IL-10 may not have a dominant role in defective IFN-gamma production in patients with MDRTB.

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References

Kim J, Uyemura K, Van Dyke M, Legaspi A, Rea T, Shuai K . A role for IL-12 receptor expression and signal transduction in host defense in leprosy. J Immunol. 2001; 167(2):779-86. DOI: 10.4049/jimmunol.167.2.779. View

Wei X, Leung B, Niedbala W, Piedrafita D, Feng G, Sweet M . Altered immune responses and susceptibility to Leishmania major and Staphylococcus aureus infection in IL-18-deficient mice. J Immunol. 1999; 163(5):2821-8. View

Wolf S, Temple P, Kobayashi M, Young D, Dicig M, Lowe L . Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol. 1991; 146(9):3074-81. View

Wahl S . Transforming growth factor beta (TGF-beta) in inflammation: a cause and a cure. J Clin Immunol. 1992; 12(2):61-74. DOI: 10.1007/BF00918135. View

de Waal Malefyt R, Yssel H, Roncarolo M, Spits H, De Vries J . Interleukin-10. Curr Opin Immunol. 1992; 4(3):314-20. DOI: 10.1016/0952-7915(92)90082-p. View

Goble M, Iseman M, Madsen L, Waite D, Ackerson L, Horsburgh Jr C . Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. N Engl J Med. 1993; 328(8):527-32. DOI: 10.1056/NEJM199302253280802. View

Orme I, Roberts A, Griffin J, Abrams J . Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection. J Immunol. 1993; 151(1):518-25. View

Cooper A, Dalton D, Stewart T, Griffin J, Russell D, Orme I . Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med. 1993; 178(6):2243-7. PMC: 2191280. DOI: 10.1084/jem.178.6.2243. View

Flynn J, Chan J, Triebold K, Dalton D, Stewart T, Bloom B . An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med. 1993; 178(6):2249-54. PMC: 2191274. DOI: 10.1084/jem.178.6.2249. View

10.

Trinchieri G . Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood. 1994; 84(12):4008-27. View

11.

Raviglione M, Snider Jr D, Kochi A . Global epidemiology of tuberculosis. Morbidity and mortality of a worldwide epidemic. JAMA. 1995; 273(3):220-6. View

12.

Cooper A, Roberts A, RHOADES E, Callahan J, Getzy D, Orme I . The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection. Immunology. 1995; 84(3):423-32. PMC: 1415123. View

13.

Flynn J, GOLDSTEIN M, Triebold K, Sypek J, Wolf S, Bloom B . IL-12 increases resistance of BALB/c mice to Mycobacterium tuberculosis infection. J Immunol. 1995; 155(5):2515-24. View

14.

Okamura H, Tsutsi H, Komatsu T, Yutsudo M, HAKURA A, Tanimoto T . Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature. 1995; 378(6552):88-91. DOI: 10.1038/378088a0. View

15.

Trinchieri G, Gerosa F . Immunoregulation by interleukin-12. J Leukoc Biol. 1996; 59(4):505-11. DOI: 10.1002/jlb.59.4.505. View

16.

USHIO S, Namba M, Okura T, Hattori K, Nukada Y, Akita K . Cloning of the cDNA for human IFN-gamma-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein. J Immunol. 1996; 156(11):4274-9. View

17.

Modlin R, Barnes P . IL12 and the human immune response to mycobacteria. Res Immunol. 1995; 146(7-8):526-31. DOI: 10.1016/0923-2494(96)83027-6. View

18.

Shafer R, Bloch A, Larkin C, Vasudavan V, Seligman S, Dehovitz J . Predictors of survival in HIV-infected tuberculosis patients. AIDS. 1996; 10(3):269-72. DOI: 10.1097/00002030-199603000-00005. View

19.

McDyer J, Hackley M, WALSH T, Cook J, Seder R . Patients with multidrug-resistant tuberculosis with low CD4+ T cell counts have impaired Th1 responses. J Immunol. 1997; 158(1):492-500. View

20.

Kohno K, Kataoka J, Ohtsuki T, Suemoto Y, Okamoto I, Usui M . IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J Immunol. 1997; 158(4):1541-50. View