Identification of distinct sites of β-endorphin that stimulate lymphokine production by murine CD4+ T cells

We recently demonstrated that the opioid peptide β-endorphin (β-End) has the capacity to stimulate interleukin-2 (IL-2) and IL-4 production by murine CD4+ T cells. Since opioid peptides have been demonstrated to contain stimulatory as well as inhibitory sites, we studied peptide fragments of β- End to identify a moiety with exclusive stimulatory capacity. To this end, the effects of various opioid peptides on the production of IL-2, IL-4, IL- 6, and interferon-γ (IFN-γ) by CD4+ T cells were determined. It appeared that two peptide fragments of β-End, i.e., β-End6-31 and β-End18-31, that lack the N-terminal enkephalin part, enhanced IL-2 and IL-4 production to a similar extent as intact β-End, indicating that the N- terminal part is not involved in the stimulating effects of β-End. Also the production of IL-6 and IFN-γ was increased by these peptides. By contrast, the fragments β-End24-31 and β-End28-31 did not stimulate the production of the cytokines. Surprisingly, also α-End, which is equivalent to β-End1-16 and hence lacks the sequence comprising amino acids 18 through 31, was stimulatory. This effect was not prevented by naloxone, indicating that opioid receptors were not involved. Moreover, methionine- enkephalin (Met-Enk), which binds to opioid receptors, did not affect cytokine production. Because both α-End and β-End18-31 stimulate cytokine production by CD4+ T cells and do not overlap in sequence, it is concluded that at least two distinct sites of β-End can exert stimulating effects on cytokine production.
Chemicals/CAS: amino acid, 65072-01-7; beta endorphin, 59887-17-1; gamma interferon, 82115-62-6; interleukin 2, 85898-30-2; metenkephalin, 58569-55-4; naloxone, 357-08-4, 465-65-6; alpha-Endorphin, 61512-76-3; beta-Endorphin, 60617-12-1; Endorphins; Interferon Type II, 82115-62-6; Interleukin-2; Interleukin-4, 207137-56-2; Interleukin-6; Lymphokines; Naloxone, 465-65-6; Peptide Fragments