Production of Pyrogen by Polymorphonuclear Leukocytes During the Course of Casein‐induced Peritonitis in Rabbits

Abstract

Rabbits with casein‐induced peritonitis were febrile only during the early stage (1.5 to 12 hours) of inflammation. At that stage, peritoneal exudate cells (PEC) had preformed endogenous pyrogen (EP), while blood leukocytes and leukocytes obtained at the later stage of the inflammatory process did not. Early PEC consisted of 99% polymorphonuclear leukocytes (PMN). As early PEC and highly purified PMN (almost 100% pure) released almost identical amounts of EP, we concluded that PMN were the EP‐producing cells in the early PEC. EP from PMN of rabbits was composed of three factors with similar molecular weight (8,000 to 18,000) but different pI values (pI 7.2, 5.4, and 4.5). EP in the three fractions could not be separated from thymocyte comitogenic factor (TMF) in terms of m.w. and pI values. About 60% of EP activity and 92% of TMF activity in the culture supernatant were present in the pi 7.2 fraction. The pi 7.2 factor was weaker in EP activity and stronger in TMF activity than the other acidic fractions (pI 5.4 and 4.5). After high purification, 42 ng of the pI 7.2 factor had one unit of EP activity: one unit of TMF activity was present in 126 pg of highly purified pi 7.2 factor.

Induction of muscle weakness by local inflammation: an experimental animal model

“…The current study focuses on establishing an experimental animal model to study muscle weakness induced by the injection of a simple inflammatory agent, casein. It is known that this agent induces a strong production of local pro-inflammatory cytokines and acute phase proteins without inducing circulating cytokines [27, 28]. The present results show that casein injection induces accumulation of neutrophils and macrophages at the site of injection, demonstrating the induction of innate inflammatory responses in this model.…”

“…Previous studies have shown that this inflammatory agent does not cause systemic production of cytokines, but induces high level production of inflammatory cytokines locally [27, 28]. Interestingly, a unique feature observed in the present study is that muscle protein degradation is found in inflamed muscle without overt signs of muscle damage or injury.…”

“…Thus, our objective was to characterize the response of skeletal muscle to a localized inflammation induced by the inflammatory agent casein. Casein is an effective chemotactic agent and has been used in previous studies to induce inflammation by promoting infiltration of neutrophils into various sites in-vivo [27, 28]. …”

Localized inflammation in peripheral tissue signals the CNS for sickness response in the absence of interleukin-1 and cyclooxygenase-2 in the blood and brain

“…An early study by Kitamura et al showed that ip casein injection in rabbits induced a long-lasting febrile response without eliciting significant amounts of endogenous pyrogens in the blood (Kitamura et al, 1986), although very high levels of endogenous pyrogens were detected in the peritoneal cavity. In the present study, a striking difference between LPS and casein induced effects is illustrated by the results in Table1.…”

Fever During Localized Inflammation in Mice Is Elicited by a Humoral Pathway and Depends on Brain Endothelial Interleukin-1 and Interleukin-6 Signaling and Central EP3 Receptors

“…The milk protein casein is known to elicit inflammation and fever in animals and humans, although its mode of action is not clear (Kitamura et al, 1986;Moissidis et al, 2005). The air pouch is a closed space covered by a membrane resembling the synovial membrane of a joint that creates a mechanical barrier that retains the inflammatory stimulus and products of the inflammatory response (Edwards et al, 1981;Sedgwick et al, 1983).…”