|Kehrli Jr, Marcus|
Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/17/1997
Publication Date: N/A
Citation: N/A Interpretive Summary: An anti-inflammatory steroid was tested in vivo for its effects on a family of receptors important to regulation of immune responses. This compound, dexamethasone, was given to several groups of dairy cattle and was found to increase the number of Type II receptors for an important compound that initiates immune responses. These Type II receptors are believed to be "decoys," which then would serve to block the immune response and may thus define an important mechanism of action of steroid hormones as anti-inflammatory compounds. Future experiments will evaluate whether a similar effect is seen during natural periods of stress in dairy cows. This type of experimentation should be useful in better understanding immune function, and may ultimately reduce the use of antibiotics in cattle.
Technical Abstract: Interleukin 1 is a key player in inflammation and the immune response. The interleukin 1 family consists of three ligands (IL-1alpha, IL-1beta, and the IL-1 receptor antagonist) and two receptors (IL-1RI and IL-1RII). Previous studies suggest a dynamic relationship amongst these receptors and ligands that regulates the magnitude and extent of IL-1-mediated activities. Our laboratory has cloned and sequenced the bovine type I and II interleukin 1 receptors, and has begun to investigate their regulation in bovine leukocytes in vitro and in vivo. IL-1RI and IL-1RII mRNA levels were up-regulated in vitro by various mediators, including dexamethasone, rBoIL-4, rBoGM-CSF, and rHuTNFalpha. Conversely, IL-1RI mRNA levels were down-regulated by IFN-gamma. An in vivo study indicated that IL-1RII mRNA levels increased earlier than IL-1RI mRNA levels in dexamethasone-treated cattle. These findings suggest that early up-regulation of IL-1RII, which is a decoy receptor, may be part of the anti-inflammatory action of glucocorticoids. Our investigations suggest that anti-inflammatory agents increase expression of the biologically inactive IL-1RII, as compared with the biologically active IL-1RI, in bovine leukocytes.