Systemic Th17-like cytokine pattern in gangrenous appendicitis but not in phlegmonous appendicitis.
BACKGROUND
Increasing circumstantial evidence suggests that not all patients with appendicitis will progress to perforation and that appendicitis that resolves may be a common event. Based on this theory and on indications of aberrant regulation of inflammation in gangrenous appendicitis, we hypothesized that phlegmonous and gangrenous appendicitis are different entities with divergent immunoregulation.


METHODS
Blood samples were collected from patients with gangrenous appendicitis (n = 16), phlegmonous appendicitis (n = 21), and nonspecific abdominal pain (n = 42). Using multiplex bead arrays, we analyzed a range of inflammatory markers, such as interleukin (IL)-1ra, IL-1rbeta, IL-2, IL-6, IL-10, IL-12p70, IL-15, and IL-17; interferon-gamma; tumor necrosis factor; CXCL8; CCL2; CCL3; and matrix metalloproteinase (MMP)-1 MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MMP-13 in blood.


RESULTS
Compared with patients with phlegmonous appendicitis and nonspecific abdominal pain, the patients with gangrenous appendicitis had increased levels of the proinflammatory markers IL-6, CCL2, IL-17, MMP-8, and MMP-9 (P < or = .04 each) accompanied by increased levels of the anti-inflammatory cytokines IL-1ra and IL-10 (P < or = .02). Patients with phlegmonous appendicitis had increased levels of IL-10 only.


CONCLUSIONS
The finding of a pattern of inflammatory markers compatible with the highly inflammatory Th17 subset in sera from patients with gangrenous appendicitis, but not in phlegmonous appendicitis, supports the hypothesis that gangrenous and phlegmonous appendicitis are different entities with divergent immune regulation. Additional studies of the differential immunopathogenesis of phlegmonous and gangrenous appendicitis are warranted, as this may have important implications in the diagnosis and management of patients with suspicion of appendicitis.
Rubér
Marie
M
Department of Surgery, Faculty of Health Sciences, Linköping University, Linköping, Sweden. marie.ruber@ibk.liu.se
Andersson
Manne
M
Petersson
B Fredrik
BF
Olaison
Gunnar
G
Andersson
Roland E
RE
Ekerfelt
Christina
C
D015746:Abdominal Pain / Q000097:blood / Q000209:etiology / Q000473:pathology; D000293:Adolescent; D000328:Adult; D001064:Appendicitis / Q000097:blood* / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood; D005260:Female; D005734:Gangrene / Q000097:blood / Q000276:immunology / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood*; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood; D008875:Middle Aged; D013492:Suppuration / Q000097:blood / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
D018925:Chemokines; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020782:Matrix Metalloproteinases