Effects of Exogenous Interleukin-6 during Pseudomonas aeruginosa Corneal Infection

Abstract

Lack of interleukin-6 (IL-6) during Pseudomonas aeruginosa corneal infection leads to more severe disease with changes in neutrophil recruitment. Exogenous IL-6 leads to increased efficiency of neutrophil recruitment and reduced bacterial loads in corneal infection in both IL-6 gene knockout and wild-type mice. This may be mediated by IL-6 increasing the production of corneal macrophage inflammatory protein 2 and intercellular cell adhesion molecule 1. We conclude that effective recruitment of neutrophils into the cornea is dependent on the production of IL-6 and that early augmentation of IL-6 may be protective in corneal infection.Pseudomonas aeruginosa is a leading cause of corneal infection, often resulting in blindness (13). The host inflammatory responses, which are orchestrated by cytokines and chemokines, are critical in determining the outcome of ocular infection with P. aeruginosa (8, 10). Our studies have shown that interleukin-6 (IL-6) is important in protecting the cornea during P. aeruginosa infection (15). Its role appears to be central to the regulation of leukocyte recruitment into the avascular cornea (15). This is consistent with findings in other infection models in IL-6 gene knockout (gko) mice (6,7,12). Other studies using systemic administration of IL-6 in septic shock (3) and listeriosis (14) also support the protective role of IL-6. We have examined the effects of local administration of IL-6 on the outcome of P. aeruginosa infection of the cornea in IL-6 gko and wild-type mice. Our results indicate that effective recruitment of polymorphonuclear neutrophils (PMN) into the cornea is dependent on production of IL-6 and that early augmentation of IL-6 may be protective in corneal infection.IL-6 gko in a C57BL/6 ϫ Sv 129 background and the corresponding wild-type mice were obtained from the Jackson Laboratory (Bar Harbour, Maine). Inbred 8-week-old mice were challenged with P. aeruginosa strain 6206 as previously described (4). Solutions of murine IL-6 for injection (2) were prepared in pyrogen-free saline and were administered as 20-l subconjunctival injections containing 100 ng of IL-6. IL-6 was administered 4 h prior to challenge, at the time of challenge, and 6 h postchallenge. Control animals were injected subconjunctivally with 20 l of pyrogen-free, phosphate buffered saline (PBS) on the same schedule. Mice were sacrificed 12 h postchallenge, and their eyes were collected and either formalin fixed or stored at Ϫ70°C for the enzyme-linked immunosorbent assay and the PMN and bacterial number assays. These experiments were performed on at least 12 mice per group and repeated at least twice.

Inhibition of NUCKS Facilitates Corneal Recovery Following Alkali Burn

“…Our data on the downregulation of these inflammatory cytokines, IL1A and IL1B, were shown to follow the fine healing process in vivo. Similar mechanisms of precise regulation of inflammatory cytokines in good recovery have also been reported previously3536.…”

Role of Interleukin-6 in the Control of Acute and Chronic Giardia lamblia Infections in Mice

“…In addition to its role in IgA production, IL-6 has been shown to promote neutrophil responses in several infection models (3)(4)(5)13). However, neutrophils were not observed during G. lamblia infection of wild-type mice (2), suggesting that IL-6 has some other role in helping to control G. lamblia infections.…”

“…Significantly, 28 days postinfection, the IL-6-deficient mice all still carried large numbers of parasites while the wild-type mice had cleared their infections. However, the number of parasites at day 28 in IL-6-deficient mice was fewer than that recovered early during the infections and by day 60, parasite numbers were reduced below the limit of detection (Ͻ10 4 parasites/ mouse) in the IL-6-deficient mice. Thus, IL-6 is required early in infection to control parasites but not to control infections later on.…”

Maladaptive Role of IL-6 in Ischemic Acute Renal Failure

“…These include stimulation of neutrophil release from the bone marrow (32), prevention of neutrophil apoptosis (33), activation of neutrophils to produce toxic enzymes (34), and activation of endothelial cells to express intercellular adhesion molecule 1 and chemokines (35,36). These effects of IL-6 are confirmed by the decreased inflammatory response in transgenic knockout mice after ischemia in the lung (37), gut (7,38), or brain (6); after injections of sterile turpentine (39) or carrageen (35); and after infections.…”