title: Naloxone prevents cell-mediated immune alterations in adult mice following repeated mild stress in the neonatal period.
abstract: 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 IL-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.
authors.affiliation: Istituto Superiore di Sanità, via Regina Elena 299, 00161, Roma, Italy. alberto_loizza@iss.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Loizzo
authors.forename: Stefano
authors.initials: S
authors.lastname: Loizzo
authors.forename: Luisa
authors.initials: L
authors.lastname: Lopez
authors.forename: Antonio
authors.initials: A
authors.lastname: d'Amore
authors.forename: Paolo
authors.initials: P
authors.lastname: Renzi
authors.forename: Santi
authors.initials: S
authors.lastname: Spampinato
authors.forename: Simonetta
authors.initials: S
authors.lastname: Di Carlo
authors.forename: Antonella
authors.initials: A
authors.lastname: Bacosi
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Zuccaro
authors.forename: Roberta
authors.initials: R
authors.lastname: Pacifici
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D020738:Leptin / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013312:Stress, Physiological / Q000276:immunology* / Q000503:physiopathology; D018417:Th1 Cells / Q000378:metabolism
chemical_list: D016207:Cytokines; D020738:Leptin; D009292:Narcotic Antagonists; D009270:Naloxone