Naloxone prevents cell-mediated immune alterations in adult mice following repeated mild stress in the neonatal period

1 Mild stress plus mild pain (solvent injection) applied daily to neonatal mice induces hormonal, behavioural and metabolic changes perduring in the adult life. 2 We investigated whether daily mild stress to neonatal mice induces also long-term defined changes of immune response, and whether immune changes are prevented through repeated administration of the opioid antagonist naloxone. 3 Mild stress plus solvent injection administered from birth to the 21st postnatal day causes not only behavioural and metabolic changes, but also long-term (up to 110 days of life) splenocytes modifications, consisting in: increased release of the Th-1 type cytokines interleukin-2 (IL-2) (from an average of 346 to 788 pg ml(-1)), interferon-gamma (from 1770 to 3942) and tumour necrosis factor-alpha (from 760 to 1241); decreased release of the Th-2 type cytokines 1L-4 (from 49.1 to 28.4) and IL-10 (from 1508 to 877). Moreover, enhanced natural killer-cell activity; enhanced proliferative splenocytes properties in resting conditions and following phytohemoagglutinin and concanavalin-A stimulation are observed. Immunological, behavioural and metabolic changes are prevented by the opioid antagonist (-)naloxone (1 mg kg(-1) per day s.c., administered instead of solvent) but not by the biologically inactive enantiomorph (+)naloxone. 4 In conclusion, endogenous opioid systems sensitive to naloxone are involved in long-lasting enhancement of the Th-1 type cytokines and cell-mediated immunological response caused by repeated mild stress administered postnatally. British Journal of Pharmacology (2002).