Sessions

The widespread use of antibiotics poses a growing global concern, particularly in intensive livestock farming. High animal stocking densities and elevated production demands place considerable stress on the immune system, thereby promoting the onset and spread of infectious diseases. The aim of our study was to investigate systemic inflammatory response mechanisms in detail and to explore alternative therapeutic strategies that, due to their immunomodulatory properties, could serve as alternatives of antibiotics in anti-infective therapies.

IDR-1002, a synthetically produced, low-molecular-weight antimicrobial peptide (AMP) known for its complex immunomodulatory activity, was applied as a potential candidate for modulating inflammatory responses. In addition to untreated controls, IDR-1002 was administered at concentrations of 10, 30, and 90 µg/ml, both solely and in combination with lipopolysaccharide (LPS, 30 µg/ml) derived from Escherichia coli. Following a 24-hour incubation period, cellular metabolic activity was assessed using the CCK-8 assay. Redox homeostasis of hepatocytes was evaluated via the Amplex Red fluorometric method, assessing hydrogen peroxide (H₂O₂) levels in the culture medium. Lipid peroxidation was determined by measuring malondialdehyde (MDA) concentrations in cell lysates using a colorimetric assay. The levels of inflammatory cytokines (GM-CSF, IL-1β, IL-6, IL-8) secreted by the cell cultures were quantified using the Luminex xMAP Intelliflex multiplex platform.

IDR-1002 did not significantly impair cellular metabolic activity at any tested concentration. Treatment with IDR-1002 alone resulted in a significant reduction in H₂O₂ production at concentrations of 30 and 90 µg/ml. GM-CSF levels were decreased both by IDR-1002 alone and in combination with LPS. Notably, the concentrations of IL-1β, IL-6, and IL-8 were markedly reduced following treatment with IDR-1002 alone. These findings indicate a pronounced anti-inflammatory effect when the peptide is used by itself. However, when co-administered with LPS, IDR-1002 at all tested concentrations further enhanced the LPS-triggered increased production of IL-1β, IL-6, and IL-8.

These results suggest that IDR-1002 exerts context-dependent immunomodulatory effects: demonstrating anti-inflammatory activity when applied alone, and a pro-inflammatory, immune-stimulating effect when combined with bacterial endotoxin. Its antioxidant potential is supported by the significant reduction in H₂O₂ levels. Overall, our findings highlight the potential utility of IDR-1002 as an immunomodulatory or immunostimulatory agent in managing bacterial inflammation in porcine liver. However, further targeted studies are necessary to elucidate the precise mechanisms underlying its immunological effects.