An immune cell population that responds to beta-endorphin and is responsible for protecting nude mice from the fatal consequences of a virus infection of the central nervous system.

Reconstitution of 3- to 4-week-old BALB/c nude (nu/nu) mice with 10(7) syngeneic splenocytes, 48 h before intracerebral inoculation with a temperature-sensitive (ts) mutant of VSV (tsG31 KS5), provided protection from the fatal consequences of clinical disease in 80-90% of the infected animals. Reconstitution of animals with 10(7) splenocytes, first depleted of natural killer (NK) cells with anti-asialo GM1 and complement, also afforded protection against the infectious disease. Depletion of T-lymphocytes with anti-thy-1.2 antibody and complement, however, provided little protection with approximately 40% of the animals succumbing to the virus infection within 30 days post-infection. A single intracerebroventricular injection with 14 pM of beta-endorphin, 24 h prior to viral infection, led to an increased fatality of mice previously reconstituted with T-lymphocytes but not in animals receiving only syngeneic NK cells. The increased fatality caused by the neuropeptide was antagonized by naloxone but not beta-endorphin-(1-27). Separation of splenocyte cell populations by buoyant density centrifugation demonstrated that small race lymphocytes, and not the large granular lymphocytes, were responsible for protection of nude mice from the central nervous system infection with ts-VSV. The beta-endorphin-responsive immune cells were shown to be a minor fraction of the small race T-lymphocyte population that bear the asialo-GM1 marker.

Transferred T lymphocytes are compromised when the donor is pretreated with beta-endorphin.

A single intracerebroventricular (i.c.v.) injection of 14 pmol of beta-endorphin into 6-7-week-old BALB/c (+/+) donor mice, 24 h prior to isolation of their T lymphocytes for use for reconstitution of athymic BALB/c (nu/nu) nude mice, altered the immuno-protective effect of adoptive transfer against an intracerebral (i.c.) infection with a temperature-sensitive mutant of vesicular stomatitis virus (tsG31 KS5 VSV). Simultaneous injection of beta-endorphin and naloxone into donor animals negated the opiate effects on splenic lymphocytes. T lymphocytes, isolated from beta-endorphin-treated donors, and then depleted with anti-asialo GM1 antiserum and complement failed to demonstrate the detrimental effects of beta-endorphin.

Beta-endorphin alters the course of central nervous system disease induced by a temperature-sensitive vesicular stomatitis virus in reconstituted nude mice.

A 100 plaque forming unit (pfu) dose of a temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV), tsG31 KS5, engendered a slowly progressive paralytic central nervous system (CNS) disease that killed all BALB/c nude mice within 28 days. Reconstitution of nude mice with 10(7) syngeneic splenocytes 24 h before intracerebral inoculation with tsG31 KS5 VSV, however, protected 92% of the animals from death. When these reconstituted animals were injected intracerebroventricularly with 14 pmol of beta-endorphin 24 h after reconstitution with splenocytes and 24 h before inoculation with tsG31 KS5 VSV, only 72% of the animals survived. Furthermore, whereas 40% of the afflicted reconstituted nude mice given intracerebroventricular injections of sterile water were able to recover from the symptoms of disease, those surviving animals which received beta-endorphin were unable to do so. A single intravenous injection of 14 pmol beta-endorphin, or repeated postinfection administration of 28 pmol of beta-endorphin intravenously into nude mice reconstituted with syngeneic splenocytes, which were pretreated with beta-endorphin, did not alter the course of CNS disease induced by tsG31 KS5 VSV. The effect induced by intracerebroventricular injection of beta-endorphin was antagonized by naloxone, but not by the neuropeptide fragment beta-endorphin-(1-27). A simultaneous intracerebroventricular injection of reconstituted nude mice with 1220 pmol of naloxone and 14 pmol of beta-endorphin resulted in a 89% survival rate, and 33% of the afflicted animals were able to overcome the symptoms of the disease induced by tsG31 KS5 VSV. Intracerebroventricular injection of reconstituted nude mice with 330 pmol of beta-endorphin-(1-27) and 14 pmol of beta-endorphin resulted in a 72% survival rate and the surviving animals were unable to improve appreciably the clinical status of their disease. Injection of reconstituted nude mice with either 1220 pmol of naloxone or 330 pmol of beta-endorphin-(1-27) alone did not alter the course of the CNS disease in any way. A single intracerebroventricular injection of 29 pmol of another psychoactive peptide, [Des-Tyr]-endorphin, 24 h after reconstitution of nude mice with splenocytes and 24 h prior to infection with virus, resulted in 74% survival; and 39% of the afflicted animals were able to recover from the clinical symptoms.