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A characterization of the in vivo immunomodulation by Met-enkephalin in mice
T Marotti1, S Rabatic, J Gabrilovac
1Rudjer Boskovic Institute, Department of Experimental Biology and Medicine, Zagreb, Croatia.
Abstract:
Single intraperitoneal injections of Met-enkephalin (MENK) into CBA mice decreased the phagocytic activity of peritoneal macrophages, Con-A-induced proliferation and NK-activity of spleen cells. Conversely, in mice which had been immunized with sheep erythrocytes, treatment with MENK was associated with enhancement of phagocytosis, and no effect on lymphoid proliferation and NK-cytotoxicity of spleen cells. MENK-induced inhibition of cellular functions in nonimmunized mice was associated with a decrease of plasma ACTH level, whereas MENK-induced stimulation of phagocytosis in immunized mice was paralleled with an elevation of ACTH, suggesting a role of corticoids in immunomodulation by MENK. MENK-induced modulation (suppression and stimulation) of phagocytosis, as well as inhibition of spleen cell proliferation, was not observable in adrenalectomized mice, although a reduced NK-cytotoxicity was still present.
Insights
Met-enkephalin (MENK) affects immune cells differently based on immunization status. In non-immunized mice, MENK suppressed immune activity, while in immunized mice, it enhanced phagocytosis, suggesting a role for corticoids.
Area of Science:
- Immunology
- Neuroendocrinology
Background:
- Met-enkephalin (MENK), an endogenous opioid peptide, plays a role in modulating physiological processes.
- The immunomodulatory effects of MENK are complex and may depend on the host's immune status.
Purpose of the Study:
- To investigate the differential effects of Met-enkephalin on immune cell functions in non-immunized versus immunized mice.
- To explore the involvement of the hypothalamic-pituitary-adrenal (HPA) axis and corticoids in MENK-induced immunomodulation.
Main Methods:
- Administration of Met-enkephalin (MENK) via intraperitoneal injection to CBA mice.
- Assessment of phagocytic activity of peritoneal macrophages.
- Evaluation of Concanavalin-A (Con-A)-induced proliferation and Natural Killer (NK)-cell activity of spleen cells.
- Measurement of plasma ACTH levels.
- Studies in adrenalectomized mice to assess the role of corticoids.
Main Results:
- In non-immunized mice, MENK decreased macrophage phagocytosis, spleen cell proliferation, and NK activity.
- In sheep erythrocyte-immunized mice, MENK enhanced phagocytosis but did not affect lymphoid proliferation or NK cytotoxicity.
- MENK-induced immune suppression in non-immunized mice correlated with decreased plasma ACTH, while immune stimulation in immunized mice correlated with elevated ACTH.
- Adrenalectomy abolished MENK-induced modulation of phagocytosis and spleen cell proliferation, but NK-cytotoxicity remained reduced.
Conclusions:
- Met-enkephalin exhibits dual immunomodulatory effects, suppressing immune functions in non-immunized states and enhancing phagocytosis in immunized states.
- Corticoids, regulated by ACTH, appear to mediate MENK's immunomodulatory actions, particularly concerning phagocytosis and lymphoid proliferation.
- The adrenal gland plays a crucial role in mediating MENK's effects on the immune system, although NK-cell function may be modulated independently.