MHC class II transcription is associated with inflammatory responses in a wild marine mammal.

Inflammation is one of the most important non-specific and rapid responses that a vertebrate can elicit in response to damage or a foreign insult. To date, despite increasing evidence that the innate and adaptive branches of immunity are more intricately related than previously thought, few have examined interactions between the Major Histocompatibility Complex (MHC, a polymorphic region of the vertebrate genome that is involved with antigen presentation) and inflammation, and even less is known about these interactions in an eco-immunological context. Here, we examined the effect of MHC class II DRB gene multiplicity and transcription on phytohemagglutinin (PHA)-induced inflammation during the early stages of development of California sea lions. Neither constitutive nor expressed ZacaDRB diversity was found to be associated with pup responses to PHA at any of the stages of pup development. However, for two-month-old pups, those with a specific MHC-DRB locus (ZacaDRB-A) tended to have less efficient responsive inflammation. Transcription of distinct MHC-DRB loci was also linked to PHA-induced inflammation, with patterns that varied markedly between ages, and that suggested that ongoing infectious processes could limit the capacity to respond to a secondary challenge. Life history constraints and physiological processes associated with development of California sea lions, in conjunction with their changing pathogenic environment could explain the observed effects of MHC class II transcription on PHA-induced inflammation. To our knowledge, ours is the first study to examine the importance of expressed vs. constitutive MHC loci on inflammation in a natural population.

Activation of an inflammatory response is context-dependent during early development of the California sea lion.

Variations in immune function can arise owing to trade-offs, that is, the allocation of limited resources among costly competing physiological functions. Nevertheless, there is little information regarding the ontogeny of the immune system within an ecological context, and it is still unknown whether development affects the way in which resources are allocated to different immune effectors. We investigated changes in the inflammatory response during early development of the California sea lion (Zalophus californianus) and examined its association with body condition, as a proxy for the availability of energetic resources. We found that the relationship between inflammation and body condition varied according to developmental stage and circulating levels of leucocyte populations, a proxy for current infection. Body condition was related to the magnitude of the inflammatory response during two of the three developmental periods assessed, allowing for the possibility that the availability of pup energetic reserves can limit immune function. For older pups, the ability to mount an inflammatory response was related to their circulating levels of neutrophils and the neutrophil to lymphocyte ratio, implying that the infection status of an individual will influence its ability to respond to a new challenge. Our results suggest that trade-offs may occur within the immune system and highlight the importance of taking into account ontogeny in ecoimmunological studies.

Prolactin-derived vasoinhibins increase anxiety- and depression-related behaviors.

The hormone prolactin (PRL) regulates neuroendocrine and emotional stress responses. It is found in the hypothalamus, where the protein is partially cleaved to vasoinhibins, a family of N-terminal antiangiogenic PRL fragments ranging from 14 to 18kDa molecular masses, with unknown effects on the stress response. Here, we show that the intracerebroventricular administration of a recombinant vasoinhibin, containing the first 123 amino acids of human PRL that correspond to a 14kDa PRL, exerts anxiogenic and depressive-like effects detected in the elevated plus-maze, the open field, and the forced swimming tests. To investigate whether stressor exposure affects the generation of vasoinhibins in the hypothalamus, the concentrations of PRL mRNA, PRL, and vasoinhibins were evaluated in hypothalamic extracts of virgin female rats immobilized for 30min at different time points after stress onset. The hypothalamic levels of PRL mRNA and protein were higher at 60min but declined at 360min to levels seen in non-stressed animals. The elevation of hypothalamic PRL did not correlate with the stress-induced increase in circulating PRL levels, nor was it modified by blocking adenohypophyseal PRL secretion with bromocriptine. A vasoinhibin having an electrophoretic migration rate corresponding to 17kDa was detected in the hypothalamus. Despite the elevation in hypothalamic PRL, the levels of this hypothalamic vasoinhibin were similar in stressed and non-stressed rats. Stress reduced the rate of cleavage of PRL to this vasoinhibin as shown by the incubation of recombinant PRL with hypothalamic extracts from stressed rats. These results suggest that vasoinhibins are potent anxiogenic and depressive factors and that stress increases PRL levels in the hypothalamus partly by reducing its conversion to vasoinhibins. The reciprocal interplay between PRL and vasoinhibins may represent an effective mechanism to regulate anxiety and depression.