Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health.

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the immune system. A symposium was organized in October 2001 to explore the possibility of an association between immune dysfunction and CFS, with special emphasis on the interactions between immune dysfunction and other abnormalities noted in the neuroendocrine and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting. Data suggest that persons with CFS manifest changes in immune responses that fall outside normative ranges, but current research does not provide definitive evidence on whether these immune abnormalities are a cause or result of the illness. It has become clear that CFS cannot be understood based on single measurements of immune, endocrine, cardiovascular, or autonomic nervous system dysfunction. This panel encourages a new emphasis on multidisciplinary research into CFS.

Prophylactic clarithromycin to treat mycobacterium avium in HIV patients receiving zidovudine may significantly increase mortality by suppressing lymphopoiesis and hematopoiesis.

The increased mortality observed when human immunodeficiency virus (HIV)-infected individuals are treated with clarithromycin (CLA) as prophylaxis for disseminated infection with organisms of the Mycobacterium avium complex (MAC) suggests that CLA might possess immunosuppressive activities. To test this possibility, we assessed the immunological response of BALB/c mice following subchronic (28 days) oral administration of CLA alone or in combination with zidovudine (ZDV). Because normal hematopoiesis is needed to maintain the immune system, we also examined the effect of these drugs given individually or in combination on several hematological parameters. The major effect of administration of 500 mg/kg CLA was a marked decrease in the lymphocyte/neutrophil ratio, and the only evidence of hematotoxicity in mice treated with 240 mg/kg ZDV alone was mild macrocytic anemia. However, treatment with a combination of CLA and ZDV resulted in severe hematotoxicity, evidenced by a significant (p < 0.01) decrease in the number of circulating erythrocytes, neutrophils, and lymphocytes and a 67% drop in splenic cellularity (p < 0.01). Treatment with CLA or ZDV alone or both drugs in combination had no effect on lymphocyte function, determined by measuring the ex vivo proliferative activity of splenocytes in response to alloantigens or a B cell mitogen, lipopolysaccharide (LPS). However, because of the cellular depletion in the spleen, overall immune responses in this organ decreased significantly (p < 0.05) in mice treated with CLA plus ZDV. These data suggest that interactions between CLA and ZDV warrant further evaluation because these drugs are given in combination to persons with advanced HIV infection.