Human eosinophils synthesize and secrete interleukin-6, in vitro

Abstract

Using the technique of in situ hybridization, we have shown that resting, unstimulated, human peripheral blood eosinophils, obtained from subjects with greater than 8% eosinophilia, transcribe and translate messenger RNA (mRNA) for interleukin-6 (IL-6). After incubation for 24 hours in culture medium alone, approximately 19% of eosinophils were positive for IL-6 mRNA. This may be a reflection of their in vivo activation, but also may suggest that the gene for this cytokine is constitutively expressed in eosinophils. After stimulation with interferon gamma (IFN gamma) (500 U/mL), the percentage of IL-6- mRNA+ cells increased to 51.3%. This was accompanied by an enhancement of intensity of the hybridization signals. The specificity of the IL-6 probe and the hybridization signals was confirmed by the use of an IL-6 sense probe and RNase pretreatment of cell preparations. Evidence for the translation of IL-6 mRNA was obtained by immunocytochemical staining. Normal and activated eosinophils gave IL-6-specific immunoreactivity with a polyclonal antihuman IL-6 antibody. A higher percentage of positive cells was detected among activated eosinophils than those treated with medium alone. Using a specific immunoenzymetric assay, we detected 190.15 +/- 18.1 and 403.32 +/- 213.6 pg/mL of IL-6 in supernatants of unstimulated and IFN gamma-treated (24 and 48 hours) eosinophils, respectively. These data indicate that eosinophils are an important cellular source of IL-6.

Eosinophils: multifaceted biological properties and roles in health and disease

“…Furthermore, when stimulated with eotaxin (CCL11) or RANTES (CCL5), human eosinophils rapidly release stored IL-4 by vesicular transport to the local milieu (46). Several other cytokines and chemokines are also transcribed and ⁄ or produced by eosinophils (3,31); for example, by reverse transcriptase polymerase chain reaction, constitutive expression of IL-6 and IL-10 mRNA was detected in blood eosinophils (44,45,47,48). Eosinophils also express a proinflammatory cytokine, TNF-a, and chemokines, such as MIP-1a (CCL3) and RANTES (CCL5) (49,50).…”

The establishment of the plasma cell survival niche in the bone marrow

“…Eosinophils constitutively express the key plasma cell survival factors APRIL and IL-6, and when they are activated, they express even higher levels of these cytokines. Upon immunization, the number of eosinophils in the bone marrow increases, and these eosinophils are activated (60), as shown by their enhanced expression of the central plasma cell survival factors APRIL and IL-6, as well as of the cytokines IL-2, IL-5, and TNF-a (76)(77)(78)(79)(80)(81). With secondary immunization, a further increase in the number of eosinophils is observed, and these cells now have the capacity to secrete even larger amounts of the survival factors (60).…”

Sudden infant death syndrome, infection and inflammatory responses

“…There can be several reasons for the elevated IL-6 levels. Many cell types produce this potent protein [41][42][43][44][45][46], and elevated levels of IL-6 are found in several different conditions [47][48][49][50][51][52][53]. Bacterial products [54,55] and various viruses [56,57] stimulate IL-6 production.…”