The endogenous production of various cytokines and the infusion of exogenous cytokines can produce stereotyped """"""""flu-like"""""""" symptoms, disorders of cognition and mood, and laboratory abnormalities. For this reason, some have speculated that many of the symptoms of CFS might reflect a hyperactive immune system that chronically elaborates relatively high levels of various cytokines. At the same time, it could be argued that some of the immunologic and virologic findings that have been identified in CFS could be explained, in part, by deficient production of specific cytokines. To explore these hypotheses, we propose a systematic study of 25 patients with CFS and 25 matched healthy control subjects, on two occasions separated by 6-12 months, to measure mononuclear cell production of several cytokines and one cytokine receptor. Because the cytokines have short half-lives, measurement of serum or plasma levels may be an insensitive technique. For that reason, we will measure messenger RNA (mRNA) levels by a recently-developed quantitative polymerase chain reaction (PCR) technique developed by one of us (G.G.). To further enhance sensitivity, the cell populations that produce each cytokine will first be isolated by flow cytometry (as part of Project 1); measurement of each cytokine thus will be performed on a population of cells highly enriched for the cell types that make the cytokine in question. The specific cytokines/cytokine receptor to be measured are: interleukin-1-beta; interleukin-2, interleukin-2 receptor, interleukin-4, interleukin-6, tumor necrosis factor-alfa, and interferon-alfa. When indicated by the PCR results, plasma levels of specific cytokines also will be measured. Abnormalities in cytokine production that may be demonstrated will be correlated to the various immunological and virological studies performed in Project 1, in the same subjects and same venepuncture specimens.
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