Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus.
IL-4 has been shown to protect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). To study IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore. IL-4 production by PBMC or T cells was strongly impaired in IDDM patients at diabetes onset (p < 0.0001). The mean IL-4 response of patients in the honeymoon stage was higher than the mean of the new onset patients, but significantly lower than the control group (p = 0.01). Patients with IDDM of longer duration (>2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; however, the difference was not statistically significant. IL-4 mRNA levels were measured using competitive reverse transcription PCR. The results showed greatly reduced mRNA levels in new onset IDDM. In contrast, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM. The results suggest an imbalance of inflammatory vs anti-inflammatory cytokine production at the onset of IDDM. Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabetes by allowing the inflammatory/autoimmune process in pancreatic islets to progress.
Pediatric and Adolescent Diabetes Research and Education Foundation, Children's Hospital of Orange County, CA 92868, USA.
M A
MA
Berman
C I
CI
Sandborg
Z
Z
Wang
K L
KL
Imfeld
F
F
Zaldivar
V
V
Dadufalza
B A
BA
Buckingham
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D007375:Interleukin-1; D012333:RNA, Messenger; D015847:Interleukin-4