TREATMENT OF REFRACTORY DISSEMINATED NONTUBERCULOUS MYCOBACTERIAL INFECTION WITH INTERFERON-GAMMA - A PRELIMINARY-REPORT

Background. Studies conducted in vitro and in animals suggest that cyt okine signals to monocytes or macrophages by interferon gamma are impo rtant in the containment and clearance of disseminated nontuberculous mycobacterial infections. Methods. We studied seven patients with refr actory disseminated nontuberculous mycobacterial infections who were n ot infected with the human immunodeficiency virus. Three patients were from a family predisposed to the development of Mycobacterium avium c omplex infections; four patients had idiopathic CD4+ T-lymphocytopenia . Their infections were culture- or biopsy-proved, involved at least t wo organ systems, and had been treated with the maximal tolerated medi cal therapy. Cellular proliferation, cytokine production, and phagocyt e function were assessed in peripheral-blood cells. Interferon gamma w as administered subcutaneously two or three times weekly in a dose of 25 to 50 mu g per square meter of body-surface area in addition to ant imycobacterial medications. Clinical effects were monitored by culture s, biopsies, radiographs, and in one patient a change in the need for paracentesis. Results. In response to phytohemagglutinin, the producti on of interferon gamma by mononuclear cells from the patients was lowe r than in normal subjects (P<0.001), whereas stimulation with ionomyci n and phorbol myristate acetate led to normal production of interferon gamma in the patients. Within eight weeks of the start of interferon gamma therapy, all seven patients had marked clinical improvement, wit h abatement of fever, clearing of many lesions and quiescence of other s, radiographic improvement, and a reduction in the need for paracente sis. Conclusions. Interferon gamma in combination with conventional th erapy may be effective for some cases of refractory disseminated nontu berculous mycobacterial infection.