Endotoxin inhibition of luteinizing hormone in sheep.

Administration of endotoxin suppresses circulating concentration of luteinizing hormone (LH) in a number of species, including rats, sheep, cattle, and non-human primates. Specifically, endotoxin administration decreases circulating concentration of LH and LH pulses frequency in castrated male sheep. Endotoxin could alter circulating concentrations of LH via actions at the hypothalamus through altered GnRH production and/or release, or endotoxin could alter circulating concentrations of LH at the level of the pituitary via inhibition of LH production and release or inhibition of LH in response to GnRH. The site of endotoxin suppression of circulating concentrations of LH as well as possible mediators of endotoxin suppression of circulating concentrations of LH, including cortiocotropin-releasing hormone, arginine vasopressin, glucocorticoids, inflammatory cytokines, prostaglandins, and opioids, are discussed.

The effect of retinal autoantigens and their peptides on the inhibition of experimental autoimmune uveitis.

Experimental autoimmune uveitis is an immune-mediated inflammation of the retina and uveal tract. Such inflammation can be induced in eyes of experimental animals by inoculating them with retinal autoantigens. This animal model of uveitis closely resembles idiopathic uveitis in humans and lends itself ideally for the study of mechanisms involved in the aetiopathogenesis of uveitis and for the evaluation of methods used to control or prevent immune-mediated intraocular inflammation. In this study we used the retinal proteins S-antigen, interphotoreceptor retinoid binding protein and some synthetic peptides of S-antigen to modulate the immune response of Lewis rats. Following immunomodulation these animals did not develop uveitis when challenged with the retinal proteins. The discovery of small, non-pathogenic peptides of retinal antigens that down-regulate the immune response has relevance in developing strategies for immune intervention in human uveitis.

Identification of an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid.

Sensitisation to retinal S-antigen has been implicated in the pathogenesis of several clinical forms of posterior uveitis. S-antigen-like molecules have recently been demonstrated in the brain and choroid plexus of experimental animals. We used a panel of four monoclonal antibodies (MAbs), MAbF4-C1, MAbC10-C10, MAbA2-G5 and MAbA9-C6, which define specific epitopes in the amino, mid and carboxyl terminal portions of S-antigen in order to identify an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid (CSF). Three MAbs, MAbF4-C1, MAbC10-C10 and MAbA9-C6, localised an S-antigen-like molecule to the cytoplasm of the epithelial cells of the human choroid plexus. Polymerase chain reaction of cDNA from choroid plexus verified the presence of S-antigen homologues in the choroid plexus. The presence of an S-antigen-like molecule in the CSF was demonstrated by western blots in seven CSF samples from patients with a variety of neuropathological disorders. It is proposed that immunological cross-reactivity and biochemical similarity between retinal S-antigen and an S-antigen-like molecule in human choroid plexus and CSF could form a basis for neurological manifestations observed in certain clinical forms of uveitides.