TY - JOUR
T1 - Increased TNF-α production in response to IL-6 in patients with systemic inflammation without infection
AU - Cabrera-Rivera, Graciela L.
AU - Madera-Sandoval, Ruth L.
AU - León-Pedroza, José Israel
AU - Ferat-Osorio, Eduardo
AU - Salazar-Rios, Enrique
AU - Hernández-Aceves, Juan A.
AU - Guadarrama-Aranda, Uriel
AU - López-Macías, Constantino
AU - Wong-Baeza, Isabel
AU - Arriaga-Pizano, Lourdes A.
N1 - Publisher Copyright:
© 2022 The Author(s).
PY - 2022/8
Y1 - 2022/8
N2 - Acute systemic inflammation can lead to life-threatening organ dysfunction. In patients with sepsis, systemic inflammation is triggered in response to infection, but in other patients, a systemic inflammatory response syndrome (SIRS) is triggered by non-infectious events. IL-6 is a major mediator of inflammation, including systemic inflammatory responses. In homeostatic conditions, when IL-6 engages its membrane-bound receptor on myeloid cells, it promotes pro-inflammatory cytokine production, phagocytosis, and cell migration. However, under non-physiologic conditions, such as SIRS and sepsis, leucocyte dysfunction could modify the response of these cells to IL-6. So, our aim was to evaluate the response to IL-6 of monocytes from patients diagnosed with SIRS or sepsis. We observed that monocytes from patients with SIRS, but not from patients with sepsis, produced significantly more TNF-α than monocytes from healthy volunteers, after stimulation with IL-6. Monocytes from SIRS patients had a significantly increased baseline phosphorylation of the p65 subunit of NF-κB, with no differences in STAT3 phosphorylation or SOCS3 levels, compared with monocytes from septic patients, and this increased phosphorylation was maintained during the IL-6 activation. We found no significant differences in the expression levels of the membrane-bound IL-6 receptor, or the serum levels of IL-6, soluble IL-6 receptor, or soluble gp130, between patients with SIRS and patients with sepsis. Our results suggest that, during systemic inflammation in the absence of infection, IL-6 promotes TNF-α production by activating NF-κB, and not the canonical STAT3 pathway.
AB - Acute systemic inflammation can lead to life-threatening organ dysfunction. In patients with sepsis, systemic inflammation is triggered in response to infection, but in other patients, a systemic inflammatory response syndrome (SIRS) is triggered by non-infectious events. IL-6 is a major mediator of inflammation, including systemic inflammatory responses. In homeostatic conditions, when IL-6 engages its membrane-bound receptor on myeloid cells, it promotes pro-inflammatory cytokine production, phagocytosis, and cell migration. However, under non-physiologic conditions, such as SIRS and sepsis, leucocyte dysfunction could modify the response of these cells to IL-6. So, our aim was to evaluate the response to IL-6 of monocytes from patients diagnosed with SIRS or sepsis. We observed that monocytes from patients with SIRS, but not from patients with sepsis, produced significantly more TNF-α than monocytes from healthy volunteers, after stimulation with IL-6. Monocytes from SIRS patients had a significantly increased baseline phosphorylation of the p65 subunit of NF-κB, with no differences in STAT3 phosphorylation or SOCS3 levels, compared with monocytes from septic patients, and this increased phosphorylation was maintained during the IL-6 activation. We found no significant differences in the expression levels of the membrane-bound IL-6 receptor, or the serum levels of IL-6, soluble IL-6 receptor, or soluble gp130, between patients with SIRS and patients with sepsis. Our results suggest that, during systemic inflammation in the absence of infection, IL-6 promotes TNF-α production by activating NF-κB, and not the canonical STAT3 pathway.
KW - NF-κB p-p65
KW - mIL-6R
KW - sIL-6R
KW - sepsis
KW - systemic inflammatory response syndrome
UR - http://www.scopus.com/inward/record.url?scp=85137009154&partnerID=8YFLogxK
U2 - 10.1093/cei/uxac055
DO - 10.1093/cei/uxac055
M3 - Artículo
C2 - 35647912
AN - SCOPUS:85137009154
SN - 0009-9104
VL - 209
SP - 225
EP - 235
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 2
ER -