The Participation of Prolactin in the Immunopathology of Experimental Pulmonary Tuberculosis

Prolactin and its receptor are widely recognized for their roles in lactogenesis and galactopoiesis. However, they have also gained attention for their role in immune pathophysiology, acting as mediators of both innate and acquired immune responses and potentially playing a significant role in chronic infectious diseases such as tuberculosis.

In this study, we examined the kinetics of prolactin and its receptor during the progression of experimental pulmonary tuberculosis in BALB/c mice infected intratracheally with a high-dose Mycobacterium tuberculosis (M. tuberculosis) reference strain, H37Rv. Groups of infected mice were euthanized at various time points, and their lungs were collected to quantify gene expression of prolactin and its receptor by RT-PCR, as well as to assess cellular expression by immunohistochemistry. In vitro infection experiments with alveolar macrophages and type II pneumocyte cell lines were conducted to evaluate the effects of prolactin on bacteriolysis and the expression of various innate immune response factors. After 2 months of infection, BALB/c mice with progressive pulmonary tuberculosis were treated with ovine PRL, and the effects were assessed by measuring bacillary loads and the extent of tissue damage (pneumonia).

In vitro studies showed that prolactin increases bacterial phagocytosis in alveolar macrophages and significantly enhances the production of reactive oxygen and nitrogen species, which reduces bacillary loads. In type II pneumocytes, prolactin, under certain conditions, induces higher, though not statistically significant, expression of cathelicidin and surfactant proteins A and D. In vivo studies revealed that, during early infection (within the first week), there was high expression of prolactin and its receptor in the lungs. Immunostaining for prolactin and its receptor was observed at the early stage of infection, mainly in alveolar epithelial cells, macrophages, and lymphocytes. During the second week of infection, immunostaining showed the organization of macrophages and lymphocytes within granulomas and in the inflammatory infiltrate around blood vessels and airways, with macrophages showing the strongest staining. Over the course of progressive disease, after 1 month of infection, pulmonary prolactin production decreased, and some macrophages and lymphocytes showed minimal prolactin immunostaining, although high prolactin receptor expression persisted; 4 months later, prolactin immunostaining was observed in the bronchial epithelium. Administration of prolactin via intraperitoneal injection 2 months after infection resulted in a significant reduction in bacillary loads after 2 months of treatment, along with increased but not statistically significant expression of TNFα and IFNγ.

Prolactin and its receptors appear to contribute to immune activation during pulmonary tuberculosis, particularly in the early stages of infection. Prolactin administration during late active disease reactivates immune protection. Although we do not demonstrate the mechanisms underlying these observations, these results could serve as a basis for expanding future experimental research.