Serum interleukin 40: an innovative diagnostic biomarker for patients with systemic lupus erythematosus.

INTRODUCTION: Interleukin (IL)-40 is a recently identified cytokine with a novel role in the pathogenesis of inflammatory diseases. Since systemic lupus erythematosus (SLE) is an autoimmune disease characterised by a pro-inflammatory response, it is likely that IL-40 contributes to the underlying disease processes of this disorder. The aim of the current study was to evaluate the potential of IL-40 to act as a diagnostic biomarker for SLE. MATERIALS AND METHODS: The study included 99 patients with SLE who attended the Rheumatology Unit at Baghdad Teaching Hospital. These subjects were divided into three subgroups according to disease status: inactive, n = 33; active moderate, n = 33; and active severe, n = 33. Additionally, 33 matched controls were studied. Full medical histories, body mass index, gender and clinical disease activity, the latter evaluated with the SLE disease activity index, were collected. Laboratory parameters measured included anti-dsDNA antibodies, C3 and C4 levels, erythrocyte sedimentation rate and C-reactive protein titres. Serum IL-40 levels were quantified using an enzyme-linked immunosorbent assay. RESULTS: IL-40 levels were significantly higher in patients (12.5420 ± 3.00575 ng/L) than in controls (6.1138 ± 0.59452 ng/L; p < 0.01). Mean serum IL-40 concentration was highest in the active severe group (15.2291 ± 2.26540 ng/L) and decreased, in order of disease severity, in the remaining cohorts: active moderate, 13.0643 ± 1.23927 ng/L; inactive, 9.3325 ± 1.62807 ng/L (P < 0.01); controls, 6.1138 ± 0.59452 ng/L. Serum IL-40 levels showed excellent validity for the diagnosis of SLE with a cut-off value of ≥ 9.3 ng/ml and area under the curve of 0.987. Sensitivity, specificity and accuracy were 99%, 90.9% and 96.97%, respectively (P < 0.001). CONCLUSIONS: Serum IL-40 levels were elevated in SLE patients. It is therefore proposed that IL-40 is a novel cytokine which is associated with SLE and positively linked with disease severity.

Prophylactic administration of a combined prebiotic and probiotic, or therapeutic administration of enrofloxacin, to reduce the incidence of bacterial chondronecrosis with osteomyelitis in broilers.

Bacteria entering the bloodstream via translocation from the gastrointestinal tract spread hematogenously and can trigger bacterial chondronecrosis with osteomyelitis (BCO) by infecting osteochondrotic microfractures in the epiphyseal-physeal cartilage of the proximal femora and tibiae. In experiment 1, broilers were fed control feed or the same feed containing BacPack 2X, which includes the prebiotic IMW50 (a mannan oligosaccharide beta-glucan yeast cell wall product) plus the probiotic Calsporin (Bacillus subtilis C-3102). Broilers reared on wire flooring consistently developed higher incidences of BCO than hatchmates reared on wood shavings litter (≥24 vs. ≤4%, respectively; P=0.001). Adding BacPack 2X to the feed on d 1 through 56 delayed the age of onset and reduced the cumulative incidence of BCO on wire flooring when compared with broilers fed the control feed (24.0 vs. 40.7%, respectively; P=0.003). In experiment 2, broilers reared on wire flooring received tap water on d 1 through 62 (control group) or therapeutic levels of the potent fluoroquinolone antimicrobial enrofloxacin in the water on d 35 through 54 (enrofloxacin group). During enrofloxacin administration, half as many birds developed BCO in the enrofloxacin group when compared with the control group (8.1 vs. 19.5%, respectively, on d 35 through 54; P=0.001), whereas both groups had similar BCO incidences subsequent to withdrawing enrofloxacin on d 55 through 62 (14.8 vs. 18.2% for the enrofloxacin vs. control groups; P=0.386). Cumulative lameness incidences for d 1 through 62 were higher for the control group than for the enrofloxacin group (39.0 vs. 25.8%, respectively; P=0.003). These results demonstrate that wire flooring imposes a rigorous challenge that leads to high incidences of BCO that can be difficult to suppress, even with therapeutic doses of enrofloxacin. Prophylactically adding BacPack 2X to the feed reduced the incidence of BCO lameness by a proportion similar to that achieved with enrofloxacin, indicating that probiotics potentially can provide effective alternatives to antibiotics for reducing BCO lameness attributable to bacterial translocation and hematogenous distribution.

Bacterial chondronecrosis with osteomyelitis in broilers: influence of sires and straight-run versus sex-separate rearing.

Two experiments (E1, E2) were conducted to compare the influence of sires (sire A on dam C vs. sire B on dam C) and straight-run versus sex-separate rearing on the incidence of bacterial chondronecrosis with osteomyelitis (BCO) in broilers. Fertile eggs from commercial breeder flocks were incubated and hatched at the University of Arkansas Poultry Research Hatchery. Male and female chicks were reared together (straight-run) or separately (sex-separate) in 3 × 3 m pens on litter or flat wire flooring with 65 (E1) or 60 (E2) birds per pen. Necropsies revealed lesions that are pathognomonic for BCO in ≥98% of the birds that became lame. The SigmaStat Z-test was used to compare cumulative BCO incidences through 8 wk of age. For birds reared on litter, the incidences of BCO were low regardless of cross or sex (range: 1.7 to 5.1%; P ≥ 0.6). Within a cross and sex, rearing the broilers straight-run versus sex-separate on wire flooring did not significantly affect the incidence of BCO. Significant incidences of BCO did not develop until after d 40. Males from the sire A cross developed a higher incidence of BCO than males from the sire B cross in E1 (27 vs. 17%, respectively; P = 0.009) but not in E2 (28.5 vs. 22.6%, respectively; P = 0.141). In both experiments, males from the sire A cross developed higher incidences of BCO than females from the sire B cross (27 vs. 11.9%, in E1; 28.5 vs. 14.8%, in E2). With the sexes pooled, broilers from the sire A cross consistently developed higher incidences of BCO than broilers from the sire B cross (21.4 vs. 14.9%, P = 0.005 in E1; 26.5 vs. 18.7%, P = 0.003 in E2). High susceptibilities to both femoral head (all femoral head necrosis = 66 to 85% incidences) and tibial head (all tibial head necrosis = 81 to 96% incidences) BCO lesions were demonstrated in lame birds from both sexes and crosses. This study supports a sire influence on the susceptibility of broilers to BCO. Sire lines can be chosen to reduce BCO susceptibility when broilers are grown beyond 6 wk of age.

Susceptibility of 4 commercial broiler crosses to lameness attributable to bacterial chondronecrosis with osteomyelitis.

Growing broilers on wire flooring provides an excellent experimental model for exposing susceptibility to lameness attributable to bacterial chondronecrosis with osteomyelitis (BCO). Two independent experiments (E1, E2) were designed to compare the susceptibilities of broilers from 4 commercial crosses (W, X, Y, and Z). The standard crosses (W and Y) grow rapidly at an early age, whereas high-yield crosses (X and Z) initially tend to grow more slowly. Chicks were obtained from a commercial hatchery for E1, or were hatched at the University of Arkansas Poultry Research Hatchery for E2. Males and females were reared together (E1; n = 360/cross) or separately (E2; n = 390/cross) in 3 × 3 m pens on litter or wire flooring (wire). Necropsies revealed lesions that were pathognomonic for BCO in ≥94% of the birds that became lame. The SigmaStat Z-test was used to compare cumulative lameness incidences at 8 wk of age. For birds reared on litter, lameness incidences were low and did not differ between crosses or sexes (range: 2.2 to 4.6%; P ≥ 0.6). When males were reared on wire, their lameness incidences (by cross) were E1 = 52% for W(b); 42% for X(c); 69% for Y(a), and 44% for Z(bc); E2 = 31% for W(b); 19% for X(c); 49% for Y(a); and 25% for Z(bc). For females reared on wire, the lameness incidences were E1 = 40% for W(b), 30% for X(c), 49% for Y(a), and 28% for Z(c); E2 = 16% for W; 15% for X; 16% for Y; and 15% for Z (ns). Accordingly, the hierarchical ranking for BCO susceptibility by broiler cross was X ≤ Z ≤ W < Y for males in E1 and E2, for females in E1, and for males and females pooled in E1 and E2. Standard broiler crosses developed higher incidences of lameness than high-yield crosses, implicating an association between rapid early growth and susceptibility to BCO. Rearing the females separately on wire in E2 led to uniformly low incidences of BCO, regardless of cross. Stress-mediated immunosuppression contributes to the pathogenesis of BCO; perhaps female broilers experience less social or competitive stress when reared separately from their male hatch mates.