Host endocrine responses during tumor growth.
Transplantation of the EL-4 lymphoma to syngeneic recipients caused significant endocrine changes which occurred very early as well as late after transplantation. Among the hormonal changes induced were a biphasic increase in the level of serum corticosterone, a biphasic decrease in serum insulin levels, an early decrease in prolactin and a terminal severe deficiency in thyroxine. The mechanism by which corticosterone levels are increased immediately following tumor transplantation appears to involve post-thymic T cells. In addition, the corticosterone response after tumor transplantation seems to be restricted to syngeneic recipients and does not seem to occur with allogeneic tumor transplantation. Further, the phenomenon may require an immunogenic tumor since the relatively nonimmunogenic mammary tumor virus (MTV) induced adenocarcinoma did not increase corticosterone in syngeneic C3H/He mice. Such data are consistent with the proposition that recognition of tumor antigen by mature T cells occurs within hours of tumor transplantation. This recognition appears to be MHC restricted. Whereas mitogen stimulation of T cells produces a glucocorticoid increasing factor designated GIF (Besedovsky et al., 1985b), it is reasonable to suggest that GIF is produced in vivo as part of the T cell response to tumor antigen. GIF in turn stimulates hypophyseal release of ACTH with a subsequent release of corticosterone from the adrenal gland. The biological relevance of this physiological increase in serum levels of corticosterone was examined with respect to the anti-inflammatory phenomenon often observed after tumor transplantation. First, a concordance was noted following tumor transplantation between elevated corticosterone levels and anti-inflammation. Similarly, transplantation of the MTV induced mammary adenocarcinoma which failed to increase serum levels of corticosterone did not exhibit anti-inflammation. Consistent with the concept that corticosterone levels increase following T cell recognition of tumor antigens, it is known that anti-inflammation does not occur with weakly immunogenic tumors but does follow transplantation of moderately immunogenic tumors (Normann, 1985b; Normann et al., 1985a). Second, adrenalectomy prevented the corticosterone response to tumor transplantation and eliminated tumor associated anti-inflammation. Additional studies are necessary to determine if the increase in serum levels of corticosterone alters other parameters of the host response to tumors. Anti-inflammation was shown to occur following tumor transplantation via a corticosterone dependent pathway.(ABSTRACT TRUNCATED AT 400 WORDS)
Besedovsky
H
H
Schweizerisches Forschungsinstitut, Medizinische Abteilung, Davos, Switzerland.
del Rey
A
A
Normann
S J
SJ
D000818:Animals; D001202:Ascitic Fluid; D003345:Corticosterone / Q000097:blood*; D005260:Female; D007328:Insulin / Q000097:blood*; D008223:Lymphoma / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000503:physiopathology; D011388:Prolactin / Q000097:blood*; D051381:Rats; D013601:T-Lymphocytes; D013950:Thymus Gland / Q000637:transplantation; D013974:Thyroxine / Q000097:blood*; D014181:Transplantation Immunology; D014407:Tumor Cells, Cultured / Q000637:transplantation
D007328:Insulin; D011388:Prolactin; D013974:Thyroxine; D003345:Corticosterone