Rate of Clearance of Interleukin-1 from the Blood of Normal and Nephrectomized Rats

Abstract

Absfracf. Interleukin-I (IL-l), a macrophage product, appears to be responsible for a wide variety of changes in animals during the early stages of infection and inflammation. However, the fate of injected IL-1 has not been established. The major pathway of removal from the circulation may be through the kidney, since IL-1 can be found in urine. The IL-1 for these studies was prepared from peritoneal macrophages of rats and rabbits. The clearance rate of IL-1 was determined by measuring the activity, for increasing plasma fibrinogen or releasing bone marrow neutrophils, which remained in the blood at various times after an iv injection. Both rat and rabbit IL-1 were removed rapidly from the blood of rats. The results indicate that less than 10% of the IL-1 was cleared by the kidney. So that rats with their kidneys removed showed only a slight decrease in the clearance rate of IL-I. This suggests that excretion through the kidney does not represent the major mechanism of IL-1 disposal. o 1985 Society for Expenmental Biology and Medicine.

Acute Phase Responses After Acute Liver Injury by Parital Hepatectomy in Rats As Indicators of Cytokine Release

“…The prompt 30-min fever in response to IL-1 in rats, noted previously by Stitt, Shimada and Bernheim (331, was short-lived, probably because of rapid clearance of the cytokine (30). TNF is also pyrogenic and can actually stimulate additional IL-1 release (34).…”

“…Analysis of the acute-phase responses in recipient rats at 30 min, 1 hr and 4 hr after injection, respectively, was designed to detect the presence of cytokines and not LPS in the donated plasma. This method for circulating cytokine quantification has been used by several groups of investigators (30)(31)(32).…”

Serum Levels of the Soluble lnterleukin-2 Receptor Are Dependent on the Kidney Function

“…However, from an ex perimental point of view, it has been found that serum levels of IL-1 do not to any large extent depend on the kidney function [18]. For IL-1, there seem to be other major pathways for clearing than the kidneys.…”

A simple inflammation model that distinguishes between the actions of anti-inflammatory and anti-rheumatic drugs

“…Seromucoid is a mixture of a 1 acid glycoprotein, a 1 cysteine protease inhibitor and hemopexin and from in vivo experiments would appear to be mainly dependent on the IL-1 type cytokines. The analysis of the role of cytokines on in vivo induction of APPs is complicated by the cytokine-induced release of other cytokines [34], the concerted release of cytokines [35], their short half-lives [36], interaction of the cytokines/corticosteroids on the hepatocyte [37], and the presence of endogenous cytokine inhibitors [29]. In general, in vivo studies have shown cytokine controlling mechanisms of APP synthesis to be similar to the mechanisms operative in vitro [38,33].…”