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Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model.

Abstract

Acute lung injury is an inflammatory condition developed after severe sepsis in response to excessive secretion of pro-inflammatory cytokines. Doxycycline is widely reported to possess immunomodulatory activity through inhibition of various inflammatory pathways. Considering the broad spectrum of anti-inflammatory activity, protective effect of doxycycline was evaluated in clinically relevant murine polymicrobial sepsis model induced by caecal ligation and puncture (CLP). In this model, sepsis is accompanied with infection and therefore ceftriaxone at sub-protective dose was combined to retard the bacterial growth. Three hours after CLP challenge, mice were administered vehicle, ceftriaxone (100 mg/kg subcutaneously) alone and in combination with immunomodulatory dose of doxycycline (50 mg/kg, intraperitoneal) and survival were monitored for 5 days. Bacterial count in blood and peritoneal fluid along with cytokines [interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α] and myeloperoxidase (MPO) in plasma and lung homogenate were measured at 18 h post-CLP. Plasma glutathione (GSH) was also determined. Doxycycline in presence of ceftriaxone improved survival of septic mice by significantly reducing the plasma and lung pro-inflammatory cytokines and MPO levels. It also increased plasma GSH levels. Doxycycline did not improve antibacterial effect of ceftriaxone in combination, suggesting that the protective effect of doxycycline was due to its immunomodulatory activity. Doxycycline in the presence of ceftriaxone demonstrated improved survival of septic mice by modulating the immune response.

Authors+Show Affiliations

Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Marg, Aurangabad, Maharashtra, India. Wockhardt Research Centre, Aurangabad, Maharashtra, India.Wockhardt Research Centre, Aurangabad, Maharashtra, India.Wockhardt Research Centre, Aurangabad, Maharashtra, India.Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Marg, Aurangabad, Maharashtra, India. santoshmokale@rediffmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31955291

Citation

Patel, Anasuya, et al. "Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model." Inflammation, 2020.
Patel A, Khande H, Periasamy H, et al. Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model. Inflammation. 2020.
Patel, A., Khande, H., Periasamy, H., & Mokale, S. (2020). Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model. Inflammation, doi:10.1007/s10753-020-01188-y.
Patel A, et al. Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model. Inflammation. 2020 Jan 18; PubMed PMID: 31955291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model. AU - Patel,Anasuya, AU - Khande,Hemant, AU - Periasamy,Hariharan, AU - Mokale,Santosh, Y1 - 2020/01/18/ PY - 2020/1/20/entrez PY - 2020/1/20/pubmed PY - 2020/1/20/medline KW - bacterial count KW - cytokines KW - inflammation KW - polymicrobial sepsis KW - survival JF - Inflammation JO - Inflammation N2 - Acute lung injury is an inflammatory condition developed after severe sepsis in response to excessive secretion of pro-inflammatory cytokines. Doxycycline is widely reported to possess immunomodulatory activity through inhibition of various inflammatory pathways. Considering the broad spectrum of anti-inflammatory activity, protective effect of doxycycline was evaluated in clinically relevant murine polymicrobial sepsis model induced by caecal ligation and puncture (CLP). In this model, sepsis is accompanied with infection and therefore ceftriaxone at sub-protective dose was combined to retard the bacterial growth. Three hours after CLP challenge, mice were administered vehicle, ceftriaxone (100 mg/kg subcutaneously) alone and in combination with immunomodulatory dose of doxycycline (50 mg/kg, intraperitoneal) and survival were monitored for 5 days. Bacterial count in blood and peritoneal fluid along with cytokines [interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α] and myeloperoxidase (MPO) in plasma and lung homogenate were measured at 18 h post-CLP. Plasma glutathione (GSH) was also determined. Doxycycline in presence of ceftriaxone improved survival of septic mice by significantly reducing the plasma and lung pro-inflammatory cytokines and MPO levels. It also increased plasma GSH levels. Doxycycline did not improve antibacterial effect of ceftriaxone in combination, suggesting that the protective effect of doxycycline was due to its immunomodulatory activity. Doxycycline in the presence of ceftriaxone demonstrated improved survival of septic mice by modulating the immune response. SN - 1573-2576 UR - https://www.unboundmedicine.com/medline/citation/31955291/Immunomodulatory_Effect_of_Doxycycline_Ameliorates_Systemic_and_Pulmonary_Inflammation_in_a_Murine_Polymicrobial_Sepsis_Model L2 - https://doi.org/10.1007/s10753-020-01188-y DB - PRIME DP - Unbound Medicine ER -