Gamma-interferon corrects aberrant protein kinase C levels and immunosuppression in the spontaneously hypertensive rat

Abstract

The effects of gamma-interferon (γ-IFN) on protein kinase C (PKC) levels and immunosuppression in the spontaneously hypertensive rat (SHR) were examined. First, an abnormal PKC distribution was found in spleen, thymus and aorta from SHRs relative to normotensive controls. Biweekly injections of rat recombinant γ-IFN (1000 U/kg) restored basal or resting PKC levels to those found in normotensive Wistar - Kyoto (WKY) rats. We also examined the effects of in vivo γ-IFN treatment on nuclear PKC (nPKC) activation in purified, isolated splenocyte nuclei. It was found that basal nPKC levels were higher in untreated SHRs than γ-IFN SHRs or WKYs. Also, while nuclei from untreated SHRs were relatively unresponsive to various immunoactive substances and PKC activators, γ-IFN treatment significantly restored activity. Last, the proliferative response to mitogen challenge of isolated splenocytes from untreated SHRs, γ-IFN-treated SHRs and WKYs was studied. Although γ-IFN treatment did not restore the proliferative response to that of WKYs, the mitogen response was significantly enhanced by treatment with γ-IFN. The data show that γ-IFN acts to restore normal immune function and corrects aberrant PKC levels and adds to the growing body of knowledge suggesting a role for immune dysfunction in the etiology of hypertension.