Review of immunological plasma markers for longitudinal analysis of inflammation and infection in rat models

Abstract

Disease or trauma of orthopedic tissues, including osteomyelitis, osteoporosis, arthritis, and fracture, results in a complex immune response, leading to a change in the concentration and milieu of immunological cells and proteins in the blood. While C-reactive protein levels and white blood cell counts are used to track inflammation and infection clinically, controlled longitudinal studies of disease/injury progression are limited.Thus, the use of clinically-relevant animal models can enable a more in-depth understanding of disease/injury progression and treatment efficacy. Though longitudinal tracking of immunological markers has been performed in rat models of various inflammatory and infectious diseases, currently there is no consensus on which markers are sensitive and reliable for tracking levels of inflammation and/or infection. Here, we discuss the blood markers that are most consistent with other outcome measures of the immune response in the rat, by reviewing their utility for longitudinal tracking of infection and/or inflammation in the following types of models: localized inflammation/arthritis, injury, infection, and injury + infection. While cytokines and acute phase proteins such as haptoglobin, fibrinogen, and α 2 -macroglobulin demonstrate utility for tracking immunological response in many inflammation and infection models, there is likely not a singular superior marker for all rat models. Instead, longitudinal characterization of these models may benefit from evaluation of a collection of cytokines and/or acute phase proteins.Identification of immunological plasma markers indicative of the progression of a pathology will allow for the refinement of animal models for understanding, diagnosing, and treating inflammatory and infectious diseases of orthopedic tissues.

2023 International Consensus Meeting on musculoskeletal infection: Summary from the treatment workgroup and consensus on treatment in preclinical models

“…Plasma biomarkers participate in complex signaling pathways, and their expression changes over time following infection and/or inflammation. While haptoglobin, alpha 2 ‐macroglobulin, fibrinogen, tumor necrosis factor‐alpha, and CRP have demonstrated correlation with infection and inflammation in rats shortly (~1–7 days) after infection, with or without injury, data on these markers as indicators of treatment effect are limited 26 . The lack of unanimous consensus may be due to this discrepancy.…”

“…While haptoglobin, alpha 2 -macroglobulin, fibrinogen, tumor necrosis factor-alpha, and CRP have demonstrated correlation with infection and inflammation in rats shortly (~1-7 days) after infection, with or without injury, data on these markers as indicators of treatment effect are limited. 26 The lack of unanimous consensus may be due to this discrepancy. Further, as different pathogens modulate the immune response through various mechanisms which may alter bacterial load and mask treatment effect, 27 more data is needed to confirm each biomarker's effectiveness in distinguishing between infection models, and between treated and untreated groups within an infection model.…”

Serum Örnekleri̇nde Alfa-2-Makroglubuli̇n Tayi̇ni̇

“…A2MG is an acute phase protein that can be used to monitor immunological response for both inflammation and infection [12]. Thus, it is also utilized to track the progression of pathological changes in animal models to unravel the inflammatory and infectious diseases [12]. Recent studies have also shown that A2MG has increased significantly in patients who showed severe COVID-19 symptoms.…”