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IL-1 Receptor Antagonist Treatment Aggravates Staphylococcal Septic Arthritis and Sepsis in Mice.

Ali A, Na M, Svensson MN, Magnusson M, Welin A, Schwarze JC, Mohammad M, Josefsson E, Pullerits R, Jin T - PLoS ONE (2015)

Bottom Line: Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury.However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

ABSTRACT

Background: Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.

Aims: To study whether IL-1Ra treatment deteriorates Staphylococcus aureus (S. aureus) septic arthritis and sepsis in mice.

Method: NMRI mice were treated with anakinra (IL-1Ra) daily for 7 days before intravenous inoculation with S. aureus strain Newman in both arthritogenic and lethal doses. The clinical course of septic arthritis, histopathological and radiological changes of the joints, as well as the mortality were compared between IL-1Ra treated and control groups.

Results: IL-1Ra treated mice developed more frequent and severe clinical septic arthritis. Also, the frequency of polyarthritis was significantly higher in the mice receiving IL-1Ra therapy. In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls. Importantly, the mortality of IL-1Ra treated mice was significantly higher than PBS treated controls.

Conclusion: IL-1Ra treatment significantly aggravated S. aureus induced septic arthritis and increased the mortality in these mice.

No MeSH data available.


Related in: MedlinePlus

IL-1Ra treated mice had more histological signs of septic arthritis.NMRI mice inoculated with S. aureus Newman strain (1.1–1.7 × 106 cfu/mouse) were treated with anakinra (IL-1 Ra 4mg/mouse, n = 30), or PBS (n = 25) every day starting on day 7 before inoculation with bacteria and continuing until the animals were sacrificed on day 10. (A) Histological evaluation (including the synovitis scores and bone erosion scores) of the joints from all 4 limbs on 10 days after infection. (B) Left panel: A micrograph of histologically intact midfoot joints from a NMRI mouse inoculated with S. aureus strain Newman that was treated with PBS. Right panel: A micrograph of a heavily inflamed midfoot joints with bone and cartilage destruction from a NMRI mouse with septic arthritis treated with anakinra. Hematoxylin/eosin was used for staining; * indicates heavely inflamed synovium; Arrow indicates the bone erosion; S, synovial tissue. Statistical evaluations were performed using the Mann–Whitney U test. Data were presented as scatter dot plot with median; ns = not significant.
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pone.0131645.g003: IL-1Ra treated mice had more histological signs of septic arthritis.NMRI mice inoculated with S. aureus Newman strain (1.1–1.7 × 106 cfu/mouse) were treated with anakinra (IL-1 Ra 4mg/mouse, n = 30), or PBS (n = 25) every day starting on day 7 before inoculation with bacteria and continuing until the animals were sacrificed on day 10. (A) Histological evaluation (including the synovitis scores and bone erosion scores) of the joints from all 4 limbs on 10 days after infection. (B) Left panel: A micrograph of histologically intact midfoot joints from a NMRI mouse inoculated with S. aureus strain Newman that was treated with PBS. Right panel: A micrograph of a heavily inflamed midfoot joints with bone and cartilage destruction from a NMRI mouse with septic arthritis treated with anakinra. Hematoxylin/eosin was used for staining; * indicates heavely inflamed synovium; Arrow indicates the bone erosion; S, synovial tissue. Statistical evaluations were performed using the Mann–Whitney U test. Data were presented as scatter dot plot with median; ns = not significant.

Mentions: In line with results from both clinical and radiological signs of septic arthritis, the histopathological changes of septic arthritis also tended to be more severe in mice receiving IL-1Ra compared to control mice. The extent of joint destruction as well as the histologically verified synovitis were enhanced in IL-1Ra treated mice compared to the PBS treated mice (Fig 3A and 3B).


IL-1 Receptor Antagonist Treatment Aggravates Staphylococcal Septic Arthritis and Sepsis in Mice.

Ali A, Na M, Svensson MN, Magnusson M, Welin A, Schwarze JC, Mohammad M, Josefsson E, Pullerits R, Jin T - PLoS ONE (2015)

IL-1Ra treated mice had more histological signs of septic arthritis.NMRI mice inoculated with S. aureus Newman strain (1.1–1.7 × 106 cfu/mouse) were treated with anakinra (IL-1 Ra 4mg/mouse, n = 30), or PBS (n = 25) every day starting on day 7 before inoculation with bacteria and continuing until the animals were sacrificed on day 10. (A) Histological evaluation (including the synovitis scores and bone erosion scores) of the joints from all 4 limbs on 10 days after infection. (B) Left panel: A micrograph of histologically intact midfoot joints from a NMRI mouse inoculated with S. aureus strain Newman that was treated with PBS. Right panel: A micrograph of a heavily inflamed midfoot joints with bone and cartilage destruction from a NMRI mouse with septic arthritis treated with anakinra. Hematoxylin/eosin was used for staining; * indicates heavely inflamed synovium; Arrow indicates the bone erosion; S, synovial tissue. Statistical evaluations were performed using the Mann–Whitney U test. Data were presented as scatter dot plot with median; ns = not significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489902&req=5

pone.0131645.g003: IL-1Ra treated mice had more histological signs of septic arthritis.NMRI mice inoculated with S. aureus Newman strain (1.1–1.7 × 106 cfu/mouse) were treated with anakinra (IL-1 Ra 4mg/mouse, n = 30), or PBS (n = 25) every day starting on day 7 before inoculation with bacteria and continuing until the animals were sacrificed on day 10. (A) Histological evaluation (including the synovitis scores and bone erosion scores) of the joints from all 4 limbs on 10 days after infection. (B) Left panel: A micrograph of histologically intact midfoot joints from a NMRI mouse inoculated with S. aureus strain Newman that was treated with PBS. Right panel: A micrograph of a heavily inflamed midfoot joints with bone and cartilage destruction from a NMRI mouse with septic arthritis treated with anakinra. Hematoxylin/eosin was used for staining; * indicates heavely inflamed synovium; Arrow indicates the bone erosion; S, synovial tissue. Statistical evaluations were performed using the Mann–Whitney U test. Data were presented as scatter dot plot with median; ns = not significant.
Mentions: In line with results from both clinical and radiological signs of septic arthritis, the histopathological changes of septic arthritis also tended to be more severe in mice receiving IL-1Ra compared to control mice. The extent of joint destruction as well as the histologically verified synovitis were enhanced in IL-1Ra treated mice compared to the PBS treated mice (Fig 3A and 3B).

Bottom Line: Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury.However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Institution of Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

ABSTRACT

Background: Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.

Aims: To study whether IL-1Ra treatment deteriorates Staphylococcus aureus (S. aureus) septic arthritis and sepsis in mice.

Method: NMRI mice were treated with anakinra (IL-1Ra) daily for 7 days before intravenous inoculation with S. aureus strain Newman in both arthritogenic and lethal doses. The clinical course of septic arthritis, histopathological and radiological changes of the joints, as well as the mortality were compared between IL-1Ra treated and control groups.

Results: IL-1Ra treated mice developed more frequent and severe clinical septic arthritis. Also, the frequency of polyarthritis was significantly higher in the mice receiving IL-1Ra therapy. In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls. Importantly, the mortality of IL-1Ra treated mice was significantly higher than PBS treated controls.

Conclusion: IL-1Ra treatment significantly aggravated S. aureus induced septic arthritis and increased the mortality in these mice.

No MeSH data available.


Related in: MedlinePlus