Time window of TNF-a in innate immunity against staphylococcal infection

Abstract: Staphylococcus aureus (S. aureus) is responsible for many human diseases including septic arthritis and sepsis shock. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in inflammation and produced mainly by macrophages and monocytes. It is believed to be involved in pathogenesis of septic arthritis. Time window of TNF-a in innate immunity against staphylococcal infection was studied in this project. Two experiments were carried out: In the first experiment mice were infected with a low dose (8x106cfu/mouse) of S. aureus to induce septic arthritis whereas in the second experiment the mice were infected with a higher dose (8x107cfu/mouse) of S. aureus to induce sepsis shock. All mice were divided into three groups. The first group was treated with anti-TNF-α 20 minutes after infection. The second group was treated with the anti-TNF-α three days after infection. The third group served as control and was injected with PBS instead of anti-TNF-α. The mice were regularly weighed and signs of arthritis and mortality were recorded. Two weeks after inoculation bacteria viable counts in different organs was done, as well as histopathological assessment of joints and measurement of cytokines in blood. We have observed that mice treated with anti-TNF-α had less severe arthritis and also less mortality. However, they had more bacteria accumulated in the kidneys and lost more weight compared to the control group. The results were mostly seen in the group early treated with TNF-α, compared to the late treated group. We conclude that anti-TNF-α might be potentially used as a therapy against septic arthritis and sepsis shock. This should be combined with antibiotics to eliminate the bacteria while the anti-TNF-α reduces the severity of the inflammation and thus reduce the risk of permanent joint destruction and mortality. We can conclude that blocking TNF-α early on is essential in order to get the best results.