Ethnicity and cytokine production gauge response of patients with hepatitis C to interferon-alpha therapy

Interferon is the primary treatment for hepatitis C virus (HCV). However, t he long-term success rate is low particularly for African Americans relativ e to Caucasians and may be due to differential immune abilities. This study compared cytokine production from PHA-stimulated peripheral blood from 25 healthy and 40 HCV-infected African Americans and Caucasians. HCV patients were designated as IFN responders or nonresponders based on outcome after t herapy. Ethnicity and genotype were associated with IFN response. IFN respo nders were 100% Caucasian, whereas nonresponders were 67% Caucasian and 33% African American: (P = 0.01). Genotype 1 was present in: 100% nonresponder s and 50% responders (P < 0.05). Age, sex, liver histology, ALT, and viral titers were equivalent (ns). Cytokine production from healthy individuals s howed ethnic variation in cytokine levels. Healthy African Americans produc ed greater amounts of IL-2 (P = 0.06), TNF-alpha (P = 0.06) and less IL-10 (P = 0.05) than healthy Caucasians. In contrast, IFN-alpha and TGF-beta lev els were equivalent. Pretherapy cytokine production among HCV patients show ed a similar pattern of ethnic variation. African American nonresponders pr oduced more IL-2 (P = 0.06) and TNF-alpha (P = 0.02) than Caucasian nonresp onders. Cytokine levels among Caucasian and African American nonresponders were equivalent (P = ns) to ethnically matched healthy individuals whereas Caucasian responders produced subnormal levels of IL-10 (P < 0.05) and TGF- beta (P < 0.05). Since all African Americans failed IFN therapy, cytokine p roduction could not be compared with therapeutic outcome. However, comparis on of cytokine production among Caucasians showed that responders produced less IL-10 (P < 0.001) and more TGF-beta (P = 0.06) than nonresponders and predicted Caucasian nonresponders with 83% sensitivity and 96% specificity. HCV genotype was not relevant to cytokine production (P = ns). Distributio n of cytokine genetic polymorphisms (TNF-alpha, TNF-beta, IL-10, TGF-alpha) was equivalent in all ethnic groups and did not predict clin:ical nonrespo nders. In summary, it appears that ethnicity may contribute to variable imm une responses and therapeutic outcome. The Cytokine profile among African A mericans suggests a more robust immune response, which may complicate thera py with IFN. In contrast, the subnormal cytokine production among, Caucasia n responders may be more permissive to IFN therapy. Pretherapy cytokine pro duction may allow prediction of drug resistance among Caucasians. (C) 2001 Wiley-Liss, Inc.