The systemic response to inflammation

Abstract

Various acute phase reactants (APR) have been studied in rats with different types of inflammation. These APR (serum albumin, serum globulins, plasma fibrinogens, serum alpha-2-glycoprotein [GP], total serum glycoproteins, serum mucoproteins) and neutrophils and lymphocytes reflect the onset, intensity, and duration of many types of experimental inflammation. The APR and cellular changes, like the inflammatory processes eliciting them, are stereotyped. Chemically induced, chronic immunologic, and delayed hypersensitivity-type acute inflammatory reactions cannot be distinguished by the APR. The most sensitive and quantitatively reliable index for the assessment of the “anti-inflammatory” action of the various steroidal and nonsteroidal drugs is the behaviour of the serum alpha-2-glycoproteins. This is also the most sensitive index of the “anti-inflammatory” action of adrenocortical steroids (or their absence, as shown in adrenalectomized rats). The various serum protein changes in rats with inflammation occur in response to greater sequestration rates at the sites of inflammation. Acute and chronic inflammation can be induced with a variety of substances affecting cell membranes (Filipin, digitonin, saponin, nystatin, d-α-tocopherol, vitamin A, and etruscomycin, to name but a few). These inflammatory reactions are inhibited in vivo by both steroidal and nonsteroidal “anti-inflammatory” drugs. We have visualized the process of inflammation as a wave of leaky membranes. The protective effects of nonsteroidal “anti-inflammatory” drugs on heat-induced and hypotonic erthrocyte lysis in vitro partially confirm the idea. The anti-arthritic effects of cytarabine (cytosine arabinoside, an immunosuppressant drug) also have been studied. Cytarabine has no systemic or local “anti-inflammatory” effect in a variety of experimental assay systems. It inhibits completely the onset of adjuvant arthritis and renders animals tolerant to further adjuvant inoculations. The APR cannot be used exclusively to distinguish between the different steroidal, non-steroidal, and immunosuppressant types of “anti-inflammatory” drugs. They are useful, however, in the overall assessment of the “anti-inflammatory” effects of drugs in all types of inflammation. The APR should be incorporated as standard procedures in laboratories “discovering” new “anti-inflammatory” drugs. Emphasis is placed on the APR as necessary requirements for the assessment of “anti-inflammatory” drugs because for example, Filipin-induced hind-paw edema can be inhibited in vivo by the i.p. administration of digitonin, another lytic agent which produces inflammation.