Two-dimensional analysis of production of IL-6 and TNF-alpha can predict the efficacy of IFN-alpha therapy.
OBJECTIVE
Many patients with chronic hepatitis C are now treated with interferon-alpha (IFN-alpha). The increase in the number of patients treated with IFN-alpha, however, has resulted in increased reports of adverse drug reactions (ADR). This prompted us to investigate for a useful parameter for predicting the effects of IFN-alpha treatment before initiating the therapy for the benefit of patients.


METHODS
Peripheral blood mononuclear cells (PBMCs) obtained from patients with chronic hepatitis C and healthy volunteers were incubated at 37 degrees C for 24 hours at various concentrations of IFN-alpha (1, 10(2), and 10(4) IU/ml). The tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) formed in the culture medium were determined. Also, the binding of 125I-labeled IFN-alpha to PBMCs and 2', 5'-oligoadenylate synthetase (2-5AS) activities were measured.


RESULTS
The addition of IFN-alpha to PBMCs at concentrations of 1-10(4) IU/ml showed dose-dependent changes in the binding of 125I-labeled IFN-alpha to PBMCs and 2-5AS activities. There was a strong correlation between the production of IL-6 and that of TNF-alpha (r>0.9). The production of IL-6 by the PBMCs of the high responders is significantly higher than that of the low-responders at the same value of TNF-alpha. A statistically significant difference was demonstrated by analysis of covariance.


CONCLUSIONS
The findings of this study suggest that two-dimensional analysis of the in vitro production of TNF-alpha and IL-6 by PBMCs induced by IFN-alpha is useful for predicting the outcome of the IFN-alpha treatment in patients.
Kawamura
C
C
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
Nakajima
S
S
Kuroki
T
T
Monna
T
T
D000328:Adult; D000368:Aged; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011379:Prognosis; D011994:Recombinant Proteins; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha