Examination of the effects of fever and anti-pyretics on Goldfish thrombocytes
Creators: Joshi, Reema
Publisher: name: University of Alberta Library
Year: 2024

<p>Ancient philosophers observed and documented fever as an increased body temperature in response to infection. Nowadays, fever is regarded as a symptom of infection and inflammation and therefore is often supressed by NSAID drugs. A common hypothesis for the benefits of a fever is that the rise in temperature hinders a pathogen’s virulence and acts as a switch to activate the body’s immune response. However, in literature, there is ongoing debate about the exact effect of fever on host health and host response to immune challenge, therefore, begging the question: does fever have net-positive or net-negative effects on host health? To answer this question, early studies utilized endothermic models placed in higher or lower temperature environments than their average core body temperature. This however, added the confound heat induced stress responses which also impacted host health and immune responses. Interestingly, fever has been conserved for millions of years, and in ectothermic species, a raise in core body temperature is achieved by relocation to warmer environments. Ectotherms such as reptiles, amphibians, fish and insects display behavioral thermoregulation. The conservation of febrile responses spans over more than 550 million years of evolution, further procuring the question about the potential benefits of fever for host health. <br>
Previous studies using teleost models have shown that behavioral fever can upregulate pro-inflammatory and anti-inflammatory gene expression at different timepoints in acute inflammation. Our lab has previously characterized enhanced immune responses in febrile conditions showing faster recruitment kinetics, altered anti-microbial profiles of effector cells and a more efficient switch from pro-inflammation to pro-resolution. While some leukocyte subsets have been examined, no teleost studies have shown the impact of fever on thrombocytes. Thrombocytes are considered “ancient platelets” and platelets in mammals have been shown to play critical roles in immune responses and possess immunomodulator capacities. While platelets were first thought to only have a role in hemostasis, they are now regarded as a dynamic cell population with versatile interactions and functions throughout the body. Thrombocytes have been observed in many ectothermic species including amphibians, reptiles, avians and fish with a high degree of conservation in cell morphology. However, aside from morphology and some studies on functional capacities of goldfish thrombocytes, little is known about thrombocyte functions within immune responses. Furthermore, while some studies have highlighted conserved functions in thrombocytes, the quantification of thrombocytes participating in the site of immune challenge is limited. While mammalian studies have long demonstrated that NSAIDs like aspirin impact platelet function, the impact of NSAID induced fever-inhibition on thrombocytes has not been explored. To examine the impact of fever-inhibition I used an established cutaneous infection model for tissue repair. Tissue repair is a tightly regulated process that relies on stages such as inflammation for pathogen clearance after tissue injury. Platelets have been long demonstrated to be crucial in tissue repair and therefore the quantification of thrombocytes in febrile and fever-inhibited conditions may highlight a potential benefit of a febrile response. <br>
Overall, my results show that fever alters the kinetics of leukocytes and thrombocytes in the peritoneum in both a natural fever and fixed temperature conditions. Febrile responses were associated with an earlier recruitment of leukocytes consisting primarily of neutrophils, followed by macrophages. Leukocytes in febrile conditions demonstrated a significant reduction in ROS and increase in NO for pathogen clearance. Furthermore, lymphocyte involvement was increased in natural fever conditions. Thrombocyte populations and proliferation was significantly reduced in the peritoneum of fish in febrile conditions compared to fixed temperature conditions. The disparity in thrombocyte population was even greater in the tissue repair model between febrile and fever-inhibited conditions. Furthermore, thrombocyte upregulation was sustained in fever-inhibited conditions compared to febrile conditions, and key pro-inflammatory and anti-inflammatory cytokines involved in tissue repair were dysregulated in fever-inhibited conditions. Finally, histological staining revealed the delay in tissue repair in fever-inhibited conditions. Taken together the data suggests a dysregulation of acute inflammatory processes by ketorolac fever-inhibition. </p>