Immunoregulatory effect of vasoactive intestinal peptide in pregnant NOD mice

VALERIA ROCA; LAROCCA L; CALAFAT M; AM FRANCHI; RAMHORST R; CP LEIROS

Simposio; Immunoregulatory effect of vasoactive intestinal peptide in pregnant NOD mice; 2007

Successful pregnancy is linked to a local proinflammatory response, switching later to aTh2 profile. Prediabetic non-obese diabetic (NOD) mice offer a suitable model to studyphysiological and pathological processes during pregnancy, since they spontaneously developa Th1 autoimmune exocrinopathy and a modest reduction in birth rate from 16weeks on. Vasoactive intestinal peptide (VIP) may play an interesting role in this model.VIP is a neuroimmunopeptide that regulates inflammatory responses by promoting Th2profiles and stimulating embryo growth. The goal of this work was to study the effectof VIP on the immune response of NOD mice. For this purpose, 16-week-old either nonpregnant (np) or pregnant at day 9 of gestation (p) NOD and BALB/c mice (control group)were used. Peritoneal macrophages from np NOD mice showed a higher proinflammatoryresponse (IL-12, nitrites, TNF-a) that was equally reversed by VIP (10-7M) in bothstrains. Pregnancy normalized NOD macrophage cytokine levels. The allogeneic responseof np NOD mice splenocytes was assayed in the presence and absence of VIP(10-7M) and progesterone (10-5M). After 4 days of culture, VIP increased thymidine uptakein the presence of progesterone in both mice strains. The combined effect of VIP onmacrophages and splenocytes was able to favor implantation. To assess whether endogenouslevels of VIP were altered in explants of NOD implantation sites, mRNA levelswere semiquantified. NOD mice showed lower levels of VIP mRNA than BALB/cmice (p