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Interaction of Met-enkephalin and corticosteroids in immunomodulation
T Marotti1, B Rocić, J Gabrilovac
1Rudjer Bosković Institute, Department of Experimental Biology and Medicine, Zagreb, Croatia.
Abstract:
The effect of Met-enkephalin (MENK) on several immune functions, corticosterone (CS) and adrenocorticotropin (ACTH) levels in the plasma was studied in adrenalectomized (ADX) and sham-adrenalectomized (SADX) mice. Multiple Met-enkephalin injections (10 mg/kg per day in two injections 12 h apart, for 4 days) increased the plaque-forming cell response to sheep erythrocytes in the spleen and enhanced the proliferation of spleen cells in vitro. These effects were comparable in sham-adrenalectomized and adrenalectomized mice. However, spleen cells of mice immunized with sheep red blood cells and injected with Met-enkephalin, showed suppressed blastogeneic transformation with Con A. The effect was equal in adrenalectomized and sham-adrenalectomized mice. In the absence of Con A in spleen cell cultures, MENK treatment of donor mice resulted in a significant mitogenic effect. NK activity of the spleen cells was suppressed in MENK-treated adrenalectomized mice. Injection of MENK decreased corticosterone levels and increased ACTH levels in the plasma of sham-adrenalectomized mice. In adrenalectomized mice plasma levels of ACTH were decreased by MENK. It seems that corticosteroid secretion, although changed by adrenalectomy and influenced by treatment with MENK, does not influence the modulatory effect of MENK on the PFC response and blastogeneic transformation of mouse spleen cells. However, NK activity of the spleen cells treated with MENK seems to the reflect joint action of MENK and corticosteroids.
Insights
Met-enkephalin (MENK) enhances immune responses like plaque-forming cells and spleen cell proliferation in mice, independent of adrenalectomy. However, it suppresses NK activity and blastogeneic transformation, suggesting complex immune modulation.
Area of Science:
- Immunology
- Neuroendocrinology
- Pharmacology
Background:
- Met-enkephalin (MENK) is an endogenous opioid peptide with known immunomodulatory effects.
- The role of corticosteroids in MENK's immune modulation is not fully understood.
- Adrenalectomy (ADX) provides a model to study hormone-independent effects.
Purpose of the Study:
- To investigate the effects of MENK on immune functions in adrenalectomized (ADX) and sham-adrenalectomized (SADX) mice.
- To determine the influence of corticosteroids on MENK's immunomodulatory actions.
- To examine MENK's impact on plasma corticosterone (CS) and adrenocorticotropin (ACTH) levels.
Main Methods:
- Mice underwent either ADX or SADX procedures.
- Multiple daily injections of MENK (10 mg/kg) were administered for four days.
- Immune functions assessed included plaque-forming cell (PFC) response, spleen cell proliferation, blastogeneic transformation (with Con A), and Natural Killer (NK) cell activity.
- Plasma CS and ACTH levels were measured.
Main Results:
- MENK treatment significantly increased PFC response and spleen cell proliferation in both ADX and SADX mice.
- MENK suppressed blastogeneic transformation with Con A, an effect consistent across both groups.
- MENK exhibited mitogenic effects on spleen cells in the absence of Con A.
- NK activity was suppressed in MENK-treated ADX mice.
- MENK decreased plasma CS and increased ACTH in SADX mice, while decreasing ACTH in ADX mice.
Conclusions:
- Corticosteroid secretion does not appear to mediate MENK's effects on PFC response and spleen cell blastogeneic transformation.
- MENK's modulatory effects on these immune parameters are largely independent of the adrenal axis.
- NK activity modulation by MENK may involve a combined action with corticosteroids.
- MENK exerts complex, context-dependent immunomodulatory effects.