Modulation of delayed-type hypersensitivity responses in hairless guinea pigs by peptides derived from enkephalin.
Although opioid peptides such as methionine (met)-enkephalin have been previously shown to enhance or suppress immune responses, few studies in animal models have addressed the immunomodulatory activity of their metabolic derivatives. Hairless (IAF/HA-HO) guinea pigs immunized with Freund's complete adjuvant containing Mycobacterium tuberculosis and repeatedly skin tested with purified protein derivative of tuberculin (PPD) display high levels of stable delayed-type hypersensitivity (DTH) to PPD. Met-enkephalin (YGGFM) and two of its metabolites (YGG, YG) enhanced and accelerated PPD-elicited DTH inflammatory reactions when injected together with elicitor in these animals. At 24 h, 5 x 10(-3) pmol met-enkephalin significantly enhanced DTH responses by 30% over PPD alone, while 5 x 10(-5) pmol of YGG and 5 x 10(-9) pmol of YG significantly enhanced these responses by 62 and 32%, respectively. At much higher doses (5 x 10(3) pmol), met-enkephalin and its metabolites significantly suppressed DTH reactions by 25-32%. Tyrosine and glycine had no effect on PPD-elicited DTH. All DTH reactions (control, enhanced, suppressed) displayed typical perivascular mononuclear cell infiltrates. We conclude that the immunoactivity of met-enkephalin resides in its first two amino acids and suggest that cleavage of enkephalin molecules to YG occurs in serum and/or on the cell surface.
Sizemore
Robert C
RC
Department of Biological Sciences, Alcorn State University, Alcorn State, Miss. 39096, USA. sizemore@lorman.alcorn.edu
Piva
Marta
M
Moore
LeeTerry
L
Gordonov
Natalia
N
Heilman
Edward
E
Godfrey
Henry P
HP
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004744:Enkephalin, Methionine / Q000819:agonists* / Q000276:immunology; D005998:Glycine / Q000276:immunology / Q000494:pharmacology; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D014373:Tuberculin / Q000276:immunology / Q000494:pharmacology; D014443:Tyrosine / Q000276:immunology / Q000494:pharmacology
D018836:Inflammation Mediators; D010455:Peptides; D014373:Tuberculin; D014443:Tyrosine; D004744:Enkephalin, Methionine; D005998:Glycine