Human acid-labile interferon alpha

In acquired immune deficiency syndrome (AIDS) and autoimmune diseases, like systemic lupus erythematosus (SLE), persisting high levels of interferon (IFN) are detectable in plasma. The IFN has been identified as an unusual human acid-labile IFN-alpha (al-IFN-alpha). Its properties are similar to that of the known alpha interferons except sensitivity to acid treatment (pH 2) which is characteristic for IFN-gamma. The nature of al-IFN-alpha is not known. Four hypotheses have been presented that suggested that: a) al-IFN-alpha may be a product of a distinct IFN gene; b) or a posttranscriptionally modified IFN-alpha molecule; c) the phenomenon of al-IFN-alpha may be an effect of synergistic action of a mixture of acid-stable IFN-alpha and acid-labile IFN-gamma; d) or the effect may be a result of an interaction of acid-stable IFN-alpha with an unknown factor(s) present in plasma and associated with progression of HIV infection or autoimmune diseases. Neither of the hypotheses have been experimentally proven. To verify the most probable hypothesis of the synergistic interactions between the acid stable and labile IFNs, the experiments with the artificial mixtures of nHuIFN-alpha and rHuIFN-gamma were performed. The synergistic effect was abolished by the treatment either with pH 2 or with anti-IFN-gamma antibodies. The residual activity was similar in both cases and corresponded to acid-stable IFN-alpha. However, al-IFN-gamma (AIDS serum with high IFN level) was found to be much more sensitive to acid treatment and only negligible effect of anti-IFN-gamma serum was observed. It suggests that the synergistic effect may be only slightly responsible for the phenomenon of acid lability of IFN-alpha. For explanation of the occurrence of al-IFN-alpha the hypothesis of existence of a factor(s) interacting with IFN-alpha should be taken into consideration.