Aspirin modulates interleukin-3 production

Additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome

P. Fishman, E. Falach-Vaknin, B. Sredni, P. L. Meroni, C. Rudniki, Y. Shoenfeld

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Objective. The granulocyte macrophage colony stimulating factors (GMCSF) and interleukin-3 (IL-3) are defined as positive signals for pregnancy, since they support the process of trophoblast invasion and expansion and induce placental growth and development. Aspirin and IL-3 were shown to be effective in preventing the manifestations of experimental antiphospholipid antibody syndrome (APS). Aspirin inhibits the activity of the enzyme cyclooxygenase in macrophages, which leads to a shift in the arachidonic acid metabolism toward the lipoxygenase pathway, and results in overproduction of leukotrienes. Our data indicated that leukotrienes are capable of stimulating IL-3 production in vitro. Our aim was to examine whether aspirin may exert its beneficial effect in APS not only by its ability to prevent thromboxane A2 production and prostaglandin I2 (PGI2) formation, but also by stimulating IL-3 production. Methods. Splenocytes and macrophages from naive mice were cultured in vitro with low dose aspirin. Nordihydroguaiaretic acid (NDGA), an inhibitor of 5-lipoxygenase, was added to mixed cultures of splenocytes and macrophages containing low dose aspirin. IL-3 production was observed. Results. When splenocytes and macrophages were cultured in vitro with low dose aspirin (10 μg/nl), a marked stimulation of IL-3 production was noted. When NDGA was added to the mixed cultures of splenocytes and macrophages containing low dose aspirin, it decreased the IL-3 production. Higher doses of aspirin did not affect the cytokine production. When splenocytes were incubated without the addition of exogenous macrophages, no stimulation of IL-3 production was noted. However, when purified leukotriene B4 or leukotriene C4 was added, there was an increase of 71 and 261%, respectively, in the stimulation of IL-3 production (p <0.01). These results were supported by in vivo studies, in which a higher serum IL-3 level was detected in mice fed low dose aspirin, compared to the control group and to mice fed a higher dose of aspirin. Conclusion. Aspirin acts as a potent stimulator of IL-3 through its ability to raise leukotriene production, which induces production of IL-3 both in vitro and in vivo.

Original languageEnglish
Pages (from-to)1086-1090
Number of pages5
JournalJournal of Rheumatology
Volume22
Issue number6
Publication statusPublished - 1995

Fingerprint

Antiphospholipid Syndrome
Interleukin-3
Aspirin
Macrophages
Leukotrienes
Masoprocol
Lipoxygenase Inhibitors
Placentation
Leukotriene C4
Thromboxane A2
Leukotriene B4
Lipoxygenase
Trophoblasts
Epoprostenol
Granulocyte-Macrophage Colony-Stimulating Factor
Prostaglandin-Endoperoxide Synthases
Growth and Development
Arachidonic Acid

Keywords

  • antiphospholipid syndrome
  • aspirin
  • interleukin-3
  • leukotrienes

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Aspirin modulates interleukin-3 production : Additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome. / Fishman, P.; Falach-Vaknin, E.; Sredni, B.; Meroni, P. L.; Rudniki, C.; Shoenfeld, Y.

In: Journal of Rheumatology, Vol. 22, No. 6, 1995, p. 1086-1090.

Research output: Contribution to journalArticle

Fishman, P. ; Falach-Vaknin, E. ; Sredni, B. ; Meroni, P. L. ; Rudniki, C. ; Shoenfeld, Y. / Aspirin modulates interleukin-3 production : Additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome. In: Journal of Rheumatology. 1995 ; Vol. 22, No. 6. pp. 1086-1090.
@article{08b3c5ccba174448ab0aed0d4e5dd3e6,
title = "Aspirin modulates interleukin-3 production: Additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome",
abstract = "Objective. The granulocyte macrophage colony stimulating factors (GMCSF) and interleukin-3 (IL-3) are defined as positive signals for pregnancy, since they support the process of trophoblast invasion and expansion and induce placental growth and development. Aspirin and IL-3 were shown to be effective in preventing the manifestations of experimental antiphospholipid antibody syndrome (APS). Aspirin inhibits the activity of the enzyme cyclooxygenase in macrophages, which leads to a shift in the arachidonic acid metabolism toward the lipoxygenase pathway, and results in overproduction of leukotrienes. Our data indicated that leukotrienes are capable of stimulating IL-3 production in vitro. Our aim was to examine whether aspirin may exert its beneficial effect in APS not only by its ability to prevent thromboxane A2 production and prostaglandin I2 (PGI2) formation, but also by stimulating IL-3 production. Methods. Splenocytes and macrophages from naive mice were cultured in vitro with low dose aspirin. Nordihydroguaiaretic acid (NDGA), an inhibitor of 5-lipoxygenase, was added to mixed cultures of splenocytes and macrophages containing low dose aspirin. IL-3 production was observed. Results. When splenocytes and macrophages were cultured in vitro with low dose aspirin (10 μg/nl), a marked stimulation of IL-3 production was noted. When NDGA was added to the mixed cultures of splenocytes and macrophages containing low dose aspirin, it decreased the IL-3 production. Higher doses of aspirin did not affect the cytokine production. When splenocytes were incubated without the addition of exogenous macrophages, no stimulation of IL-3 production was noted. However, when purified leukotriene B4 or leukotriene C4 was added, there was an increase of 71 and 261{\%}, respectively, in the stimulation of IL-3 production (p <0.01). These results were supported by in vivo studies, in which a higher serum IL-3 level was detected in mice fed low dose aspirin, compared to the control group and to mice fed a higher dose of aspirin. Conclusion. Aspirin acts as a potent stimulator of IL-3 through its ability to raise leukotriene production, which induces production of IL-3 both in vitro and in vivo.",
keywords = "antiphospholipid syndrome, aspirin, interleukin-3, leukotrienes",
author = "P. Fishman and E. Falach-Vaknin and B. Sredni and Meroni, {P. L.} and C. Rudniki and Y. Shoenfeld",
year = "1995",
language = "English",
volume = "22",
pages = "1086--1090",
journal = "Journal of Rheumatology",
issn = "0315-162X",
publisher = "Journal of Rheumatology",
number = "6",

}

TY - JOUR

T1 - Aspirin modulates interleukin-3 production

T2 - Additional explanation for the preventive effects of aspirin in antiphospholipid antibody syndrome

AU - Fishman, P.

AU - Falach-Vaknin, E.

AU - Sredni, B.

AU - Meroni, P. L.

AU - Rudniki, C.

AU - Shoenfeld, Y.

PY - 1995

Y1 - 1995

N2 - Objective. The granulocyte macrophage colony stimulating factors (GMCSF) and interleukin-3 (IL-3) are defined as positive signals for pregnancy, since they support the process of trophoblast invasion and expansion and induce placental growth and development. Aspirin and IL-3 were shown to be effective in preventing the manifestations of experimental antiphospholipid antibody syndrome (APS). Aspirin inhibits the activity of the enzyme cyclooxygenase in macrophages, which leads to a shift in the arachidonic acid metabolism toward the lipoxygenase pathway, and results in overproduction of leukotrienes. Our data indicated that leukotrienes are capable of stimulating IL-3 production in vitro. Our aim was to examine whether aspirin may exert its beneficial effect in APS not only by its ability to prevent thromboxane A2 production and prostaglandin I2 (PGI2) formation, but also by stimulating IL-3 production. Methods. Splenocytes and macrophages from naive mice were cultured in vitro with low dose aspirin. Nordihydroguaiaretic acid (NDGA), an inhibitor of 5-lipoxygenase, was added to mixed cultures of splenocytes and macrophages containing low dose aspirin. IL-3 production was observed. Results. When splenocytes and macrophages were cultured in vitro with low dose aspirin (10 μg/nl), a marked stimulation of IL-3 production was noted. When NDGA was added to the mixed cultures of splenocytes and macrophages containing low dose aspirin, it decreased the IL-3 production. Higher doses of aspirin did not affect the cytokine production. When splenocytes were incubated without the addition of exogenous macrophages, no stimulation of IL-3 production was noted. However, when purified leukotriene B4 or leukotriene C4 was added, there was an increase of 71 and 261%, respectively, in the stimulation of IL-3 production (p <0.01). These results were supported by in vivo studies, in which a higher serum IL-3 level was detected in mice fed low dose aspirin, compared to the control group and to mice fed a higher dose of aspirin. Conclusion. Aspirin acts as a potent stimulator of IL-3 through its ability to raise leukotriene production, which induces production of IL-3 both in vitro and in vivo.

AB - Objective. The granulocyte macrophage colony stimulating factors (GMCSF) and interleukin-3 (IL-3) are defined as positive signals for pregnancy, since they support the process of trophoblast invasion and expansion and induce placental growth and development. Aspirin and IL-3 were shown to be effective in preventing the manifestations of experimental antiphospholipid antibody syndrome (APS). Aspirin inhibits the activity of the enzyme cyclooxygenase in macrophages, which leads to a shift in the arachidonic acid metabolism toward the lipoxygenase pathway, and results in overproduction of leukotrienes. Our data indicated that leukotrienes are capable of stimulating IL-3 production in vitro. Our aim was to examine whether aspirin may exert its beneficial effect in APS not only by its ability to prevent thromboxane A2 production and prostaglandin I2 (PGI2) formation, but also by stimulating IL-3 production. Methods. Splenocytes and macrophages from naive mice were cultured in vitro with low dose aspirin. Nordihydroguaiaretic acid (NDGA), an inhibitor of 5-lipoxygenase, was added to mixed cultures of splenocytes and macrophages containing low dose aspirin. IL-3 production was observed. Results. When splenocytes and macrophages were cultured in vitro with low dose aspirin (10 μg/nl), a marked stimulation of IL-3 production was noted. When NDGA was added to the mixed cultures of splenocytes and macrophages containing low dose aspirin, it decreased the IL-3 production. Higher doses of aspirin did not affect the cytokine production. When splenocytes were incubated without the addition of exogenous macrophages, no stimulation of IL-3 production was noted. However, when purified leukotriene B4 or leukotriene C4 was added, there was an increase of 71 and 261%, respectively, in the stimulation of IL-3 production (p <0.01). These results were supported by in vivo studies, in which a higher serum IL-3 level was detected in mice fed low dose aspirin, compared to the control group and to mice fed a higher dose of aspirin. Conclusion. Aspirin acts as a potent stimulator of IL-3 through its ability to raise leukotriene production, which induces production of IL-3 both in vitro and in vivo.

KW - antiphospholipid syndrome

KW - aspirin

KW - interleukin-3

KW - leukotrienes

UR - http://www.scopus.com/inward/record.url?scp=0029077576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029077576&partnerID=8YFLogxK

M3 - Article

VL - 22

SP - 1086

EP - 1090

JO - Journal of Rheumatology

JF - Journal of Rheumatology

SN - 0315-162X

IS - 6

ER -