Interactions between the nervous and immune systems have became a focus of attention from the view point of physiological and pathological consequences. Several Lines of evidence indicate that hormones of neural origin, particulary opioid peptides, are involved in the regulation of immune cell function. Pharmacologic studies indicate that some cells of the immune system have opioid receptors, though not yet well characterized. Direct opioid effects on cells of the immune system have been reported. Numerous effects on immune system function have been reported after systemic administration of opioids. Some of the in vivo effects are opposite to the directly demonstrated in vitro effects. These may well be of physiologic or pathophysiologic importance, but mechanism of actions of opioid peptides remain obscure. The main goal of our proposed study is to evaluate the action of opioid peptides on immune cell function period. This study would delineate molecular mechanism involved in neural opioid peptide modulation of immune effector cells(such as T and B cells). The preliminary work has been done on the particular fraction of mouse splenic B lymphocytes stimulated with lipopolysaccharide (LPS) or LPS/Dextran sulfate(LPS/DxS) in the presence of met-enkephalin(ME) and proenkephalin (PRO-ENK). The amount and isotype of antibody secreted by this cultured cells was determined. These mitogenic stimuli were chosen since LPS and LPS/DxS respectively, stimulate either one-third or majority of B cells to differentiate. Increasing concentrations of ME and Pro-Enk(10-16 to 10-18 M) were added to cultures at 0,3,6, and 24 h after mitogen. At all time points of ME addition, LPS/DxS stimulation shifted the dose response curve for inhibition of IgM secretion to lower concentrarions of ME as compared to cells stimulated with LPS alone. This inhibition in IgM production by ME returned to control levels at 10-8 M. In LPS/DxS stimulated cells only a concomitant biphasic decrease in IgG3 production occured after all time point of ME addition and no changes occuredd with LPS alone. No significant changes occured with IgG1 and IgG2a production. On the other hand, Pro-Enk increased the production of IgG1 and IgG2a at the doses from at 0h in LPS stimulated B-cell, whereas no significant changes occured in IgG3 and IgM production. Both ME and PRO-ENK have no effect on mitogen-induced B-cell Proliferation. The reults indicate that the precursor molecule and its procesed peptide differentially affect B cell functions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES090072-02
Application #
3755522
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code