Augmentation of TNF-alpha production, NK cell activity and IL-12 p35 mRNA expression by methionine enkephalin.
OBJECTIVE
To study the host immune surveillance functions by the neuropeptide methionine enkephalin (met-enk).


METHODS
To measure the effects of met-enk on NK activity, the production and gene expression of anti-tumor cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-12 (IL-12) in vitro and in vivo.


RESULTS
Met-enk promoted NK activity at 1 x 10(-8) - 1 x 10(-5) mol.L-1, increased TNF-alpha production both in vitro and in vivo, and enhanced IL-12 p35 gene transcription after ip 0.1 mg.kg-1 for 6 d.


CONCLUSIONS
The up-regulating effects of met-enk contribute to the host neuro-immunomodulating mechanism against tumors and invading antigens. Enkephalins and endorphins were originally described as the endogenous ligands for the morphine receptors in the brain. In addition to their central nervous activity, an immunomodulating action of the enkephalins was first reported in 1979. Methionine enkephalin (met-enk) regulated a variety of immunological responses, including enhancing the proliferation of human peripheral lymphocytes and mouse spleen cells, regulating antibody production, natural killer cells (NK) activity and synthesis of a number of cytokines. These results suggested that met-enk might be used to elevate the body resistance to cancer and other diseases, or diminish autoimmune responses which are detrimental to host. To elucidate that met-enk has the activity of anti-tumor through related immune regulating responses, this study is to investigate the effects of met-enk on immune surveillance and immune defence functions.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
F
F
Zhong
X Y
XY
Li
S L
SL
Yang
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D018664:Interleukin-12 / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D004744:Enkephalin, Methionine