thymic-humoral-factor-gamma-2 and Chronic-Disease

We investigated the antiviral and immunomodulatory effects of a combination treatment using thymus humoral factor-gamma 2 and alpha-interferon in patients with chronic hepatitis B in whom previous monotherapy with interferon had failed.. Nine HBeAg and HBV-DNA seropositive patients received thymus humoral factor-gamma 2 alone for 2 months, thymus humoral factor-gamma 2 plus alpha-interferon for 2 months and finally alpha-interferon alone for 2 months.. Treatment with thymus humoral factor-gamma 2 alone was not associated with any side effects. The interferon-induced lymphopenia was significantly less marked during the combined therapy in comparison to the previous course with interferon alone (mean reduction of lymphocyte counts 33.5 +/- 11.6% versus 56.3 +/- 16.7%, respectively, p < 0.05). The combination of thymus humoral factor-gamma 2 plus interferon showed a significantly more profound inhibition of serum HBV-DNA (mean reduction from the pretreatment level 90.6 +/- 13.3%) compared to the earlier monotherapy with interferon in the same patients (mean reduction 55.5 +/- 34.7%, p < 0.01). As a result of the combined thymus humoral factor-gamma 2 plus alpha-interferon regimen three out of nine patients became HBV-DNA negative and seroconverted to anti-HBe. Thymus humoral factor-gamma 2 appears to exert mainly a functional effect on T lymphocytes, as interleukin-2 production was increased in the majority of treated patients, whilst the expression of lymphocyte activation markers remained unchanged.. These data suggest that thymus humoral factor-gamma 2 may be useful in a combined therapeutic approach in chronic HBV carriers.

Topics: Adult; Chronic Disease; Cytokines; DNA, Viral; Drug Combinations; Drug Therapy, Combination; Female; Hepatitis B; Hepatitis B virus; Humans; Interferon-alpha; Lymphocytes; Male; Oligopeptides; Thymus Hormones; Time Factors

A recent study indicated that thymic hormones have antiviral effects in human hepatitis B virus infection and woodchuck hepatitis virus infection. These hormones are known to exert immunomodulatory effects on lymphocyte maturation and function; because these are abnormal in patients with chronic hepatitis B virus infection, we have examined the effects of a thymic hormone (THF gamma 2) on peripheral blood mononuclear cells from patients with chronic hepatitis B virus infection. THF gamma 2 (50 or 150 ng/ml) alone was without effect; in the presence of low doses of the mitogen phytohaemagglutinin, it had a broad effect in patients and controls. The effect on interleukin-2 production was greater in patients than controls with a significant increase in production at 150 ng/ml for patients alone (p = 0.037). Tumour necrosis factor alpha production was enhanced in all patients and controls, with a greater effect seen at 150 ng/ml THF gamma 2 than 50 ng/ml. There was no effect on interferon gamma production or on the expression of membrane markers of T-cell activation. THF gamma 2 has substantial immunomodulatory activity in chronic hepatitis B virus carriers and in vivo assessment of THF gamma 2 in chronic hepatitis B virus is indicated.

Topics: Antigens, CD; Antigens, CD1; Cells, Cultured; Chronic Disease; Cytokines; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Hepatitis B; HLA-DR Antigens; Humans; Interferon-gamma; Interleukin-2; Interleukin-6; Leukocytes, Mononuclear; Oligopeptides; Phytohemagglutinins; Thymus Hormones; Tumor Necrosis Factor-alpha