TO THE EDITOR:
We read with interest the recent report on the National Institutes of Health conference on interferon-
in the management of infectious diseases. Aside from its use in the treatment of chronic granulomatous disease, interferon- is considered to be important in treating certain intracellular infections such as leishmaniasis, toxoplasmosis, and infections by atypical mycobacteria and Mycobacterium leprae [1]. These infections seem to be characterized by a preponderance of a TH2-type immune response that has a direct inhibitory effect on TH1 cells. This effect leads to interferon- deficiency and diminished host defense reactions in patients [2]. Recent data on interferon- gene or receptor "knock-out" mice support this conclusion and justify administration of interferon- to patients.
We do not question the usefulness of interferon- therapy but want to illuminate the underlying immune state that differs from the TH1/TH2 paradigm. Examination of the immune status of patients with such infections shows that their cellular immune system is highly activated. For example, increased levels of circulating interferon- and of the interferon--inducible factor neopterin were described in patients with leishmaniasis [3] related to M. tuberculosis [4] and M. leprae [5] infection, whereby the degree of elevation correlates with the severity of the disease. In fact, TH1 cells appear to be chronically activated. Feedback regulatory mechanisms of effector cells may counteract their microbicidal abilities and could explain why these cells can no longer destroy the pathogens. Down-regulation of cell surface receptors for interferon- may further explain why only high doses of interferon- enhance the activity of effector cells such as macrophages, which are necessary for the destruction of intracellular pathogens.
1. Gallin JI, Farber JM, Holland SM, Nutman TB. Interferon- in the management of infectious diseases. Ann Intern Med. 1995; 123:216-24.
2. Romagnani S, Del Prete G, Manetti R, Ravina A, Annunziato F, DeCarli M, et al. Role of TH1/TH2 cytokines in HIV infection. Immunol Rev. 1994; 140:73-92.
3. Zwingenberger K, Harms G, Pedrosa, Cortez PM, Sandkamp B, Scheibenbogen C. Generation of cytokines in human visceral leishmaniasis: dissociation of endogenous TNF-
and IL-1 ß production. Immunobiology. 1001; 183:125-32.
4. Fuchs D, Hausen A, Kofler M, Kosanowski H, Reibnegger G, Wachter H. Neopterin as an index of immune response in patients with tuberculosis. Lung. 1984; 162:337-46.
5. Schmutzhard E, Fuchs D, Hausen A, Reibnegger G, Wachter H. Is neopterin a marker of cell mediated immune response helpful in classifying leprosy. East Afr Med J. 1986; 63:577-80.
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