Tumor necrosis factor alpha activity in genital tract secretions of guinea pigs infected with chlamydiae

Abstract

Previous studies using the guinea pig model of chlamydial genital infection demonstrated that primary infection is associated with a marked acute inflammatory response early on, while chronic inflammation appears later, at a time when the level of infection is reduced. Challenge infections result primarily in a chronic inflammatory response. The stimuli that initiate inflammation and lead to tissue damage have not been defined. We investigated the possibility that tumor necrosis factors (TNFs) play a role in the inflammatory response to chlamydial genital tract infection. Cytotoxicity assays for TNF were performed on genital tract secretions collected from female guinea pigs during infection with the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis. During the early days of primary infection, high levels of TNF-␣ were detected in genital tract secretions from inbred S2 strain and outbred Hartley strain guinea pigs. Significantly lower levels of TNF-␣ were detected in secretions from both strains during challenge infection. In general, the intensity of the TNF-␣ response was proportional to the intensity of infection. High TNF-␣ levels were present during primary infection at a time of marked neutrophil influx. Thus, TNF-␣ may play an important role in the response to primary chlamydial genital tract infection.

Mouse strain-dependent variation in the course and outcome of chlamydial genital tract infection is associated with differences in host response

“…It can induce a significant influx of neutrophils and has a strong activating effect on these cells, in addition to other leukocytes and endothelial cells. We have documented high levels of TNF-␣ in the genital tract secretions of guinea pigs during primary chlamydial infection at a time of marked neutrophil influx (4).…”

Scarring trachoma is associated with polymorphism in the tumor necrosis factor alpha (TNF-alpha) gene promoter and with elevated TNF-alpha levels in tear fluid

“…Studies on chlamydial infection in animal models indicate that TNF-␣ levels reflect the intensity of current infection (14) and may cause tissue damage which leads to scarring (34). The likely additional role of TNF-␣ in the fibrogenic process of scar formation (25,33) has not yet been investigated in experimental models of chlamydial disease.…”

“…Conversely, TNF-␣ may protect against active chlamydial infection, as it has an antichlamydial effect both in vitro (29,30) and in vivo against the C. trachomatis mouse pneumonitis agent in the lung (35). Secretion of TNF-␣ occurs at the genital site of C. psittaci infection in guinea pigs (14), although its relevance to protection is unknown.…”

Role of Polymorphonuclear Neutrophils in a Murine Model ofChlamydia psittaci-Induced Abortion

“…TNF-␣ measurement. Because previous data have suggested that PMNs are a significant source of tumor necrosis factor alpha (TNF-␣) (5,38) and since TNF-␣ has frequently been documented as an initiatory cytokine released upon chlamydial invasion of the host (12), the presence of this cytokine in the sera of both depleted and nondepleted mice was determined to establish whether PMNs were the source of TNF-␣ in our infection model. To determine the presence of TNF-␣ in response to chlamydial infection, serum samples were collected from mice at different days p.i.…”