Administration of gamma interferon in human subjects decreases plasminogen activation and fibrinolysis without influencing C1 inhibitor

Abstract

Recombinant gamma interferon (rHuIFN-gamma) has been recognized to increase mRNA and protein levels of C1 inhibitor (C1 INH) in various human cells. Further, when administered to patients with colon cancer, it increased plasma C1 INH levels. A prospective trial was initiated to determine whether rHuIFN-gamma could elevate plasma C1 INH levels in six normal volunteers and two patients with type I angioedema. After 1 month of observation of plasma C1 INH levels, rHuIFN-gamma was administered subcutaneously at 25 micrograms/M2 daily for 4 consecutive days. All healthy volunteers and patients experienced local erythema, headache, myalgias, and chills during the administration of rHuIFN-gamma. C1 INH, prekallikrein, high-molecular-weight kininogen, and factor XII levels in plasma were not influenced by the rHuIFN-gamma administration. One patient with hereditary angioedema (HAE) had an attack of angioedema 3 days after completion of rHuIFN-gamma therapy. During the attack, circulating cleaved high-molecular-weight kininogen, kallikrein-alpha 2-macroglobulin complexes, and an altered 50 kd form of kallikrein were detected in the patient's plasma. Additional studies showed that rHuIFN-gamma treatment resulted in decreased total fibrinolytic activity. It was found that immediately after rHuIFN-gamma treatment, tissue plasminogen activator activity and antigen levels were not significantly decreased in volunteers. Plasminogen activator inhibitor levels rose significantly, but this activity was not due to plasminogen activator inhibitor-1 antigen, whose value significantly fell. These data suggest that rHuIFN-gamma may stimulate the expression of another plasminogen activator inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)