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Interferon-γ and Management of Infectious Diseases
- Steven M. Holland, MD;
- Joshua M. Farber, MD; and
- John I. Gallin, MD
- National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, MD 20189
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IN RESPONSE:
We agree with Baier-Bitterlich and colleagues that the mechanism by which interferon-γ acts in the setting of chronic infections such as leishmaniasis or tuberculosis is complex and may not fit neatly into the TH1/T H2 paradigm. Feedback loops, such as that which includes prostaglandin E2, are known to be down-regulatory for the destruction of intracellular pathogens at the macrophage level and are overcome by pharmacologic interferon-γ administration [1]. Similarly, interleukin-6 has been shown to down-regulate macrophage tumor necrosis factor-α receptor levels and to antagonize the interferon-γ-induced up-regulation of tumor necrosis factor-α receptor levels [2]. The general finding, however, has been that patients who progress to severe, disseminated infection with intracellular parasites such as Mycobacterium leprae or leishmania usually have abnormal lymphocyte proliferation and low interferon-γ production in response to antigen; these conditions return to normal after successful therapy [3, 4].
The broad question raised by Baier-Bitterlich and colleagues concerns the underlying mechanisms of interferon-γ in its pharmacologic versus its physiologic effects. Many physiologic effects of interferon-γ have been carefully described [5], but those that are significantly responsible for the effect of the agents in a given in vivo setting, such as an infection, remain unclear. Experiments with interferon-γ “knock-out” mice have confirmed the central physiologic importance of interferon-γ in controlling and eliminating intracellular pathogens. However, because we are still unsure of the mechanisms responsible for eliminating these infections, we cannot assess the specific critical effects of interferon-γ in these settings.
Many paths lead to serious infection—some host determined, some organism determined. Many paths (host-, organism-, or physician-determined) also eliminate infection. The ways in which interferon-γ reduces the incidence of infections in chronic granulomatous disease or assists in clearing certain mycobacterial and parasitic infections when administered therapeutically remain to be discovered.
Steven M. Holland, MD
Joshua M. Farber, MD
John I. Gallin, MD
National Institute of Allergy and Infectious Diseases
National Institutes of Health Bethesda, MD 20189
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
