Impact of dual neutralization of TNF-α and IL-1β along with Gentamicin treatment on the functions of blood and splenic neutrophils and its role on improvement of S. aureus induced septic arthritis

Int Immunopharmacol. 2023 Oct:123:110766. doi: 10.1016/j.intimp.2023.110766. Epub 2023 Aug 10.

Abstract

Researches of recent past years have emphasized potential of antibiotics to improve septic arthritis but as multi-drug resistant strains like MRSA are emerging fast, new alternative therapeutic advances are high in demand. This study aims to figure out the role of neutrophils in regulating inflammatory responses of S. aureus induced septic arthritis while using TNF-α Ab or IL-1β Ab along with antibiotic gentamicin or both in combination. In this study, role of anti-oxidant enzymes were investigated and correlated with generated ROS level. While expression of TLR2, TNFR2, MMP2, RANKL, SAPK/JNK in the spleen were evaluated through western blot. Serum activity of IL-8, IL-10, IL-12, OPG, OPN, CRP was assessed using ELISA. Flow cytometry study evaluated inflamed neutrophil population. Results have shown TNF-α neutralization along with gentamicin was able to reduce arthritic swelling prominently. While combination therapy effectively reduced blood neutrophil ROS activity, arginase activity, MPO activity along with spleen bacterial burden. Serum OPG, CRP, IL-10 level got reduced while serum OPN, IL-8 and IL-12 level enhanced in treatment groups, showing mitigation of inflammatory damage. Overall, it is a novel work that observed how antibiotic and antibody therapy enhanced neutrophil function positively to combat sepsis. This study may not be fully applicable in clinical trials as it is performed with animal model. Clinical trials include crystalline and inflammatory arthritides, trauma, neoplasm. Interdisciplinary collaboration between radiology, orthopaedic surgery and knowledge of animal system responses may give better idea to find proper therapeutic approach in future research works.

Keywords: Anti-oxidant enzymes; Gentamicin; S. aureus; Septic arthritis.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Arthritis, Infectious* / drug therapy
  • Cytokines / metabolism
  • Gentamicins / therapeutic use
  • Interleukin-10 / metabolism
  • Interleukin-12
  • Interleukin-8
  • Methicillin-Resistant Staphylococcus aureus*
  • Neutrophils / metabolism
  • Reactive Oxygen Species
  • Spleen / metabolism
  • Staphylococcus aureus / physiology
  • Tumor Necrosis Factor-alpha

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Cytokines
  • Gentamicins
  • Interleukin-8
  • Reactive Oxygen Species
  • Interleukin-12
  • Anti-Bacterial Agents