Showing papers by "Charles A. Dinarello published in 1981"

Demonstration of a circulating suppressor factor of thymocyte proliferation during endotoxin fever in humans.

Abstract: Sub-pyrogenic levels of human leukocytic pyrogen (LP) have been shown to enhance phytohemagglutinin-induced murine thymocyte proliferation. It was concluded that LP is similar to lymphocyte-activating factor (LAF). Since endotoxin stimulates the production of LP and LAF, we attempted to employ in vitro thymocyte proliferation to detect circulating LP/LAF in 12 normal human subjects during experimental endotoxin fever. Sera obtained before and during fever were first mixed with an immunoadsorbent that binds human LP/LAF, and then the dissociated material was added to thymocyte cultures. Material derived from sera obtained during the maximum fever (3 to 4 hr after endotoxin) was markedly suppressive for thymocyte proliferation in vitro. The appearance of this suppressive effect correlated with the profound lymphopenia observed in the subjects. This suppressor factor(s) was nondialyzable and was destroyed at 70 degrees C, and its suppressive effects inhibited the lymphocyte-activating property of LP/LAF. In addition, the suppression of PHA responses did not appear to be modulated by prostaglandin synthesis. The results demonstrate that a factor circulates during endotoxin fever in humans that suppresses in vitro thymocyte proliferation.

Production of Leukocytic Pyrogen from Phagocytes of Neonates

Abstract: To study the lack of fever during the human newborn period, cord blood leukocytes obtained at birth were stimulated to produce leukocytic pyrogen (LP) in vitro. Phagocytic leukocytes from infants who were born by Caesarean section and whose mothers had not experienced natural onset of labor produced no LP or significantly less LP than leukocytes from adults or from infants born after natural onset of labor. There was a significant difference between total white blood cell count in cord blood of infants whose phagocytic cells produced LP and those whose cells did not. This observation could not be accounted for by anesthetic agents, phagocytosis of staphylococci, or number of leukocytes producing LP; thus, they suggest an intrinsic defect in the ability to produce LP before birth. Of interest is that a nondialyzable substance(s) present in crude preparations of human chorionic gonadotropin markedly suppressed LP production from adult human monocytes, but purified human chorionic gonadotropin had no effect.