Can experienced surgeons predict the additional value of a CT scan in patients with displaced intra-articular distal radius fractures?

There are no clear guidelines when an additional CT scan should be obtained for the treatment of displaced intra-articular distal radius fractures (DRF). This study aimed to investigate whether surgeons can predict the usefulness of CT scans to facilitate choice of treatment plan and/or pre-operative planning for DRF. Four surgeons evaluated 51 patients with displaced DRF. The choice of treatment (operative or nonoperative) was based on conventional radiographs. Subsequently, the surgeons were asked whether they would have requested an additional CT scan to determine this treatment choice, and also whether they required a CT scan for pre-operative planning. After 4 weeks, the additional CT scan was provided and the cases were assessed again. Based on these data, we calculated the number needed to scan (NNS) and number needed to harm (NNH) for two decision models. Model 1: Only provide a CT scan if the surgeon requested one based on their judgment of the X-rays. Model 2: CT scans for all displaced intra-articular DRF. For choice of treatment, the NNS was lower for model 1 than for model 2 (2.6 vs. 4.3) and the NNH is higher for model 1 (3.1 vs. 1.3). For pre-operative planning, the NNS (1.3 vs. 1.4) and NNH (3.7 vs. 3.4) were comparable for both models. Surgeons are able to predict the usefulness of an additional CT scan for intra-articular displaced DRF for OR indication. However, for pre-operative planning the usefulness of a CT scan is much harder to predict.

Aerobic training-induced improvements in arterial stiffness are not sustained in older adults with multiple cardiovascular risk factors.

There is a well-established relationship between increased arterial stiffness and cardiovascular mortality. We examined whether a long-term aerobic exercise intervention (6 months) would increase arterial compliance in older adults with hypertension complicated by Type 2 diabetes (T2DM) and hyperlipidemia. A total of 52 older adults (mean age 69.3±0.6 years, 30 males and 22 females) with diet/oral hypoglycemic-controlled T2DM, hypertension and hypercholesterolemia were recruited. Subjects were randomly assigned to one of two groups: an aerobic group (6 months vigorous aerobic exercise, AT group) and a non-aerobic group (6 months of no aerobic exercise, NA group). Arterial stiffness was measured as pulse-wave velocity (PWV) using the Complior device. Aerobic training decreased arterial stiffness as measured by both radial (P=0.001, 2-way analysis of variance with repeated measures) and femoral (P=0.002) PWV. This was due to a decrease in arterial stiffness in the AT group after 3 months of training, which was not maintained after 6-month training for either radial (P=0.707) or femoral (P=0.680) PWV. Our findings indicate that in older adults with multiple cardiovascular risk factors, short-term improvements in arterial stiffness became attenuated over the long term.

Role of enteric nerves in immune-mediated changes in protease-activated receptor 2 effects on gut function.

BACKGROUND: Protease-activated receptors (PARs) are expressed on structural and immune cells. Control of initiation, duration, and magnitude of PAR effects is linked to the level of receptor expression, availability of proteases, and the intracellular signal transduction machinery. We investigated nematode infection-induced changes in PAR(2) expression and the impact on smooth muscle and epithelial responses to PAR(2) agonists. METHODS: Smooth muscle and epithelial cell function were assessed in wild-type, and IL-4, IL-13 or STAT6 gene-deficient mice following treatment with vehicle, Nippostrongylus brasiliensis or Heligmosomoides polygyrus, or IL-13. The role of enteric nerves was determined using tetrodotoxin to block nerve conduction. Expression of PAR(2) was assessed by real-time PCR, western blot and immunohistochemistry. KEY RESULTS: Nematode infection induced a STAT6- and IL-13-dependent up-regulation of PAR(2) mRNA expression. The infection-induced hypercontractility to PAR(2) agonists required STAT6/IL-13 and was neurally mediated. In contrast, the infection-induced decrease in epithelial secretion to PAR(2) agonists was partly dependent on STAT6 and independent of enteric nerves. The hyposecretion was correlated with decreased PAR(2) immunofluorescent staining on the apical surface of epithelial cells, but enhanced lamina propria immunostaining for PAR(2). CONCLUSIONS & INFERENCES: This is the first study to demonstrate an immune regulation of PAR(2) expression that impacts both smooth muscle and epithelial cell responses to PAR(2) agonists. Differences in responses between smooth muscle and epithelial cells are related to the contribution of enteric nerves. These data provide a mechanism by which activation of PAR(2) in immune-based pathologies can induce both transient and long-lasting changes in gut function.

Micromotor endoscope catheter for in vivo, ultrahigh-resolution optical coherence tomography.

A distally actuated, rotational-scanning micromotor endoscope catheter probe is demonstrated for ultrahigh-resolution in vivo endoscopic optical coherence tomography (OCT) imaging. The probe permits focus adjustment for visualization of tissue morphology at varying depths with improved transverse resolution compared with standard OCT imaging probes. The distal actuation avoids nonuniform scanning motion artifacts that are present with other probe designs and can permit a wider range of imaging speeds. Ultrahigh-resolution endoscopic imaging is demonstrated in a rabbit with <4-microm axial resolution by use of a femtosecond Cr:forsterite laser light source. The micromotor endoscope catheter probe promises to improve OCT imaging performance in future endoscopic imaging applications.

AAVP Symposium: new approaches in the study of animal parasites.

The following three papers are a very small window onto the types of research being pursued by members of the American Association of Veterinary Parasitologists. They are related by the fact that newer areas in the biology of parasites and their hosts are discussed. The first paper by Dr. Tom Klei, gives a brief view of the interactions between host and parasite of the fascinating organism Wolbachia, a parasite of parasites. The second paper by Dr. Gloria Solano-Aguilar addresses the use of probiotics to alter the host­parasite interface and influence host resistance. The final paper by Dr. Lou Gasbarre outlines an example of integration of the genomics revolution into Veterinary Parasitology. While the subjects are diverse, they demonstrate the vitality of the AAVP.

Cutting edge: IL-4 receptor expression by non-bone marrow-derived cells is required to expel gastrointestinal nematode parasites.

Expulsion of two gastrointestinal nematode parasites, Nippostrongylus brasiliensis and Trichinella spiralis, is similar in that both require IL-4Ralpha expression, but different in that T cells and mast cells are required for IL-4-induced expulsion of T. spiralis but not N. brasiliensis. To examine the role of IL-4Ralpha signaling in immunity to these parasites, we studied worm expulsion in chimeric mice that selectively expressed IL-4Ralpha on bone marrow-derived or non-bone marrow-derived cells. N. brasiliensis was expelled by mice that expressed IL-4Ralpha only on non-bone marrow-derived cells, but not by mice that expressed IL-4Ralpha only on bone marrow-derived cells. Although T. spiralis expulsion required IL-4Ralpha expression by both bone marrow- and non-bone marrow-derived cells, IL-4 stimulation eliminated the requirement for IL-4Ralpha expression by bone marrow-derived cells. Thus, direct IL-4Ralpha signaling of nonimmune gastrointestinal cells may be generally required to induce worm expulsion, even when mast cell and T cell responses are also required.

The role of IL-4 in Heligmosomoides polygyrus-induced alterations in murine intestinal epithelial cell function.

IL-4 and IL-13 promote gastrointestinal worm expulsion, at least in part, through effects on nonlymphoid cells, such as intestinal epithelial cells. The role of IL-4/IL-13 in the regulation of intestinal epithelial function during Heligmosomoides polygyrus (Hp) infection was investigated in BALB/c mice infected with Hp or treated with a long-lasting formulation of recombinant mouse IL-4/alphaIL-4 complexes (IL-4C) for 7 days. Separate groups of BALB/c mice were drug-cured of initial infection and later reinfected and treated with anti-IL-4R mAb, an antagonist of IL-4 and IL-13 receptor binding, or with a control mAb. Segments of jejunum were mounted in Ussing chambers, and short circuit current responses to acetylcholine, histamine, serotonin, PGE2, and glucose were determined. Although only modest changes in epithelial cell function were observed during primary Hp infection, IL-4C or a secondary Hp infection each induced more dramatic changes, including increased mucosal permeability, reduced sodium-linked glucose absorption, and increased Cl- secretory response to PGE2. Some, but not all, effects of IL-4C and Hp infection were dependent on enteric nerves. Hp-induced changes in epithelial function were attenuated or prevented by anti-IL-4R mAb. Thus, IL-4/IL-13 mediate many of the effects of Hp infection on intestinal epithelial cell function and do so both through direct effects on epithelial cells and through indirect, enteric nerve-mediated prosecretory effects. These immune system-independent effector functions of IL-4/IL-13 may be important for host protection against gastrointestinal nematodes.

A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist.

IL-22 is an IL-10 homologue that binds to and signals through the class II cytokine receptor heterodimer IL-22RA1/CRF2-4. IL-22 is produced by T cells and induces the production of acute-phase reactants in vitro and in vivo, suggesting its involvement in inflammation. Here we report the identification of a class II cytokine receptor designated IL-22RA2 (IL-22 receptor-alpha 2) that appears to be a naturally expressed soluble receptor. IL-22RA2 shares amino acid sequence homology with IL-22RA1 (also known as IL-22R, zcytor11, and CRF2-9) and is physically adjacent to IL-20Ralpha and IFN-gammaR1 on chromosome 6q23.3-24.2. We demonstrate that IL-22RA2 binds specifically to IL-22 and neutralizes IL-22-induced proliferation of BaF3 cells expressing IL-22 receptor subunits. IL-22RA2 mRNA is highly expressed in placenta and spleen by Northern blotting. PCR analysis using RNA from various tissues and cell lines showed that IL-22RA2 was expressed in a range of tissues, including those in the digestive, female reproductive, and immune systems. In situ hybridization revealed the dominant cell types expressing IL-22RA2 were mononuclear cells and epithelium. Because IL-22 induces the expression of acute phase reactants, IL-22RA2 may play an important role as an IL-22 antagonist in the regulation of inflammatory responses.

The role of the DMPO-hydrated electron spin adduct in DMPO-*OH spin trapping.

Time-resolved in situ radiolysis ESR (electron spin resonance, equivalently EPR, electron paramagnetic resonance) studies have shown that the scavenging of radiolytically produced hydroxyl radical in nitrous oxide-saturated aqueous solutions containing 2 mM DMPO is essentially quantitative (94% of the theoretical yield) at 100 micros after the electron pulse [1]. This result appeared to conflict with earlier results using continuous cobalt-60 gamma radiolysis and hydrogen peroxide photolysis, where factors of 35 and 33% were obtained, respectively [2,3]. To investigate this discrepancy, nitrogen-saturated aqueous solutions containing 15 mM DMPO were cobalt-60 gamma irradiated (dose rate = 223 Gy/min) for periods of 0.25-6 min, and ESR absorption spectra were observed approximately 30 s after irradiation. A rapid, pseudo-first-order termination reaction of the protonated DMPO-hydrated electron adduct (DMPO-H) with DMPO-OH was observed for the first time. The rate constant for the reaction of DMPO-H with DMPO-OH is 2.44 x 10(2) (+/- 2.2 x 10(1)) M(-1) s(-1). In low-dose radiolysis experiments, this reaction lowers the observed yield of DMPO-OH to 44% of the radiation-chemical OH radical yield (G = 2.8), in good agreement with the earlier results [2,3]. In the absence of the DMPO-H radical, the DMPO-OH exhibits second-order radical termination kinetics, 2k(T) = 22 (+/- 2) M(-1) s(-1) at initial DMPO-OH concentrations > or = 13 microM, with first-order termination kinetics observed at lower concentrations, in agreement with earlier literature reports [4].

Beta-adrenoceptor blockade alters thymocyte differentiation in aged mice.

The thymus is the primary site for generation of naive T-lymphocytes in the young animal. With age, the thymus progressively involutes and fewer mature T-cells are produced and migrate to the periphery. With thymic involution, increased density of sympathetic noradrenergic (NA) innervation and concentration of norepinephrine (NE) have been observed. To determine if the age-related changes in thymocyte differentiation are modified by NE signaling through beta-adrenergic receptors, 2-month (mo) and 18-mo old BALB/c mice were implanted subcutaneously with pellets containing the non-selective beta-adrenoceptor antagonist nadolol. Four and one-half weeks later, thymus and peripheral blood were collected to assess changes in thymocyte differentiation and naive T-cell output by flow cytometric analysis of T-cell subpopulations. In old mice, but not in young mice, thymocyte CD4/CD8 co-expression was altered by beta-adrenoceptor blockade. In nadolol-treated old mice, the frequency of the immature CD4-8- population was increased, and the intermediate CD4+8+ population was reduced. A corresponding increase in the frequency of mature CD4-8+, but not CD4+8- cells was observed. The increase in CD4-8+ cells is most likely not mediated by more CD4-8+ cells undergoing positive selection, because CD3hi expression in the CD4+8+ population was not altered by nadolol. The percentage of CD8+44low naive cells in peripheral blood increased in nadolol-treated mice, suggesting that more CD4-8+ cells were exported from the thymus to the periphery. These results indicate that the age-associated increase in sympathetic NA innervation of the thymus modulates thymocyte maturation. Pharmacological manipulation of NA innervation may provide a novel means of increasing naive T-cell output and improving T-cell reactivity to novel antigens with age.

Interleukin 20: discovery, receptor identification, and role in epidermal function.

A structural, profile-based algorithm was used to identify interleukin 20 (IL-20), a novel IL-10 homolog. Chromosomal localization of IL-20 led to the discovery of an IL-10 family cytokine cluster. Overexpression of IL-20 in transgenic (TG) mice causes neonatal lethality with skin abnormalities including aberrant epidermal differentiation. Recombinant IL-20 protein stimulates a signal transduction pathway through STAT3 in a keratinocyte cell line, demonstrating a direct action of this ligand. An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.

One-trial conditioning of the antibody response to hen egg lysozyme in rats.

In Wistar rats, reexposure to a novel conditioned stimulus (CS) previously paired with a protein antigen, hen egg lysozyme (HEL) on a single conditioning trial increased anti-HEL IgG levels relative to conditioned rats that were not reexposed to the CS, conditioned rats that were preexposed to the CS, and nonconditioned rats. These results confirm previous findings that a single exposure to a CS associated with immunization is sufficient to elicit an antibody response upon subsequent reexposure to the CS in the absence of exogenous antigen.

Prehospital and emergency department delays after acute stroke: the Genentech Stroke Presentation Survey.

BACKGROUND AND PURPOSE: Patient delays in seeking treatment for stroke and delays within the Emergency Department (ED) are major factors in the lack of use of thrombolytic therapy for stroke. The Genentech Stroke Presentation Survey was a multicentered prospective registry of patients with acute stroke. The study was designed to characterize prehospital delays and delays within the ED. METHODS: Patients with stroke symptoms presenting to 48 EDs participating in a clinical trial of acute stroke therapy were enrolled prospectively. A 1-page data form was completed from patient interviews and medical records. RESULTS: A total of 1207 subjects were entered into the study. Ninety-four percent of the 721 subjects with complete data had a diagnosis of stroke or transient ischemic attack, 13% were black, 50% were female, and 67% were aged >65 years. The median time from symptom onset to ED arrival was 2.6 (interquartile range 1.2 to 6.3) hours. The median time from ED arrival until CT scan completion was 1.1 (0.7 to 1.8) hours, and the total delay time (symptom onset until CT scan completion) had a median of 4.0 (2.3 to 8.3) hours. Patients who arrived by emergency medical services had significantly shorter prehospital delay times and times to CT scan. Age, race, sex, and educational level did not appear to affect prehospital delay times. CONCLUSIONS: Despite its limitations, this large geographically diverse study strongly suggests that the use of emergency medical services is an important modifiable determinant of delay time for the treatment of acute stroke.

Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.

Anti-tumor effect of L-deprenyl is associated with enhanced central and peripheral neurotransmission and immune reactivity in rats with carcinogen-induced mammary tumors.

L-Deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, has previously been shown to improve immune responses and restore noradrenergic (NA) nerve fibers in the spleen of old rats. In tumor-bearing rats, L-deprenyl inhibited tumor incidence and enhanced tuberoinfundibular dopaminergic (TIDA) neurotransmission in the hypothalamus. The aim of the present study was to investigate whether alterations in sympathetic NA activity and cellular immune responses in the spleen, and TIDA activity in the hypothalamus, accompany deprenyl-induced regression of 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced mammary tumors. Rats with DMBA-induced mammary tumors were treated with 0, 2.5 mg, or 5.0 mg/kg body weight of deprenyl daily for 13 weeks. Saline-treated tumor-bearing rats exhibited reduced splenic IL-2 and IFN-gamma levels, and lowered splenic norepinephrine (NE) concentration and hypothalamic dopaminergic activity, compared to rats without tumors. In contrast, treatment with 2.5 mg/kg and 5.0 mg/kg of deprenyl reduced the number and size of mammary tumors. Deprenyl-induced tumor regression was accompanied by increased immune measures in the spleen, including enhanced IL-2 and IFN-gamma production, and NK cell activity. Neural measures enhanced by deprenyl included NE concentration in the spleen and TIDA neuronal activity in the hypothalamus. These results suggest that (1) mammary tumorigenesis is associated with the inhibition of sympathetic NA activity in the spleen, TIDA activity in the hypothalamus, and cell-mediated immunity, and (2) reversal of the inhibition of catecholaminergic neuronal activities of the central nervous system and peripheral nervous system by deprenyl may enhance anti-tumor immunity.

TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease.

B cells are important in the development of autoimmune disorders by mechanisms involving dysregulated polyclonal B-cell activation, production of pathogenic antibodies, and co-stimulation of autoreactive T cells. zTNF4 (BLyS, BAFF, TALL-1, THANK) is a member of the tumour necrosis factor (TNF) ligand family that is a potent co-activator of B cells in vitro and in vivo. Here we identify two receptors for zTNF4 and demonstrate a relationship between zTNF4 and autoimmune disease. Transgenic animals overexpressing zTNF4 in lymphoid cells develop symptoms characteristic of systemic lupus erythaematosus (SLE) and expand a rare population of splenic B-Ia lymphocytes. In addition, circulating zTNF4 is more abundant in NZBWF1 and MRL-lpr/lpr mice during the onset and progression of SLE. We have identified two TNF receptor family members, TACI and BCMA, that bind zTNF4. Treatment of NZBWF1 mice with soluble TACI-Ig fusion protein inhibits the development of proteinuria and prolongs survival of the animals. These findings demonstrate the involvement of zTNF4 and its receptors in the development of SLE and identify TACI-Ig as a promising treatment of autoimmune disease in humans.

Restoration of splenic noradrenergic nerve fibers and immune reactivity in old F344 rats: a comparison between L-deprenyl and L-desmethyldeprenyl.

L-deprenyl, a monoamine oxidase-B inhibitor, partially reversed the age-associated decline in splenic sympathetic noradrenergic (NA) innervation and immune reactivity in old male rats. The purpose of the present study was to examine whether the effects of deprenyl on splenic sympathetic NA nerve fibers and immune functions are mediated through a metabolite of deprenyl, L-desmethyldeprenyl. Old male F344 rats were treated with 0, 0.25, or 1.0 mg L-(-)-deprenyl/kg BW; 0.025, 0.25, or 1.0 mg L-(-)-desmethyldeprenyl/kg BW; and 1.0 mg D-(+)-desmethyldeprenyl/kg BW i.p. daily for 8 weeks. The animals were sacrificed after a 10-day drug wash-out period and the spleens were removed for histofluorescence, immunocytochemistry, neurochemical, and immunological analysis. The volume density of NA nerve fibers was increased in the spleens of deprenyl- and L-desmethyldeprenyl-treated old rats. Con A-induced IFN-gamma production by spleen cells was elevated in 1.0 mg/kg deprenyl- and L-desmethyldeprenyl-treated rats in comparison to saline- and D-desmethyldeprenyl-treated old rats. Deprenyl and desmethyldeprenyl treatment did not alter the percentage of CD5+ T cells, but treatment with 1.0 mg/kg deprenyl and 0.025 mg/kg L-desmethyldeprenyl prevented the decline in the percentage of sIgM(+)B cells in the spleens of old rats. These results suggest that L-desmethyldeprenyl may be as equipotent as deprenyl in preventing age-associated diminution in splenic sympathetic NA innervation and immunocompetence.

DMPO-Alkyl radical spin trapping: an in situ radiolysis steady-state ESR study.

Short-lived free radicals formed in the reaction of 11 substrates and radiolytically produced hydroxyl radicals were trapped successfully with 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) in dilute aqueous solution. The in situ radiolysis steady-state ESR spectra of the spin adducts were analyzed to determine accurate ESR parameters for these spin adducts in a uniform environment. Parent alkyl radicals include methyl, ethyl, 1-propyl and 2-propyl (1-methylethyl). Hydroxyalkyl parent radicals were hydroxymethyl, hydroxyethyl, 2-hydroxy-2-propyl (1-methyl-1-hydroxyethyl), 1-hydroxypropyl and 2-hydroxy-2-methylpropyl. Carboxyl radical (carbon dioxide anion, formate radical) and sulfite anion radical were the sigma radicals studied. The DMPO spin adduct of 1-propyl was identified for the first time. For most spin adducts, g factors were also determined for the first time. In DMPO spin adducts of hydroxyalkyl radicals, nitrogen and C(2)-proton hyperfine coupling constants are smaller than those of alkyl radical adducts; the hydroxyalkyl spin adducts possess larger g values than their unsubstituted counterparts. These changes are ascribed to the spread of pi conjugation to include the hydroxyl group. Strong evidence of spin addend-aminoxyl group interaction can be seen in the asymmetrical line shapes in the hydroxyethyl and the hydroxypropyl spin adducts.

Alterations in T lymphocyte activity following chemical sympathectomy in young and old Fischer 344 rats.

In aged Fischer 344 (F344) rats, sympathetic noradrenergic (NA) innervation of the spleen is markedly diminished compared with young rats. To determine if diminished NA innervation can still provide functional signals to splenic T cells, young (3 months old) and old (17 months old) F344 rats were treated with the NA-selective neurotoxin, 6-hydroxydopamine (6-OHDA) to destroy peripheral NA nerve fibers. In 3-month-old rats, no alterations in spleen cell Con A-induced T cell proliferation, IL-2 or IFN-gamma production were observed up to 15 days after sympathectomy, when splenic NE was maximally depleted. By 21 days post-sympathectomy, when NE levels had partially recovered, Con A-induced proliferation and IFN-gamma production, but not IL-2 production, were reduced in sympathectomized animals. After day 21 post-sympathectomy, no alterations in T cell functions were observed in sympathectomized animals. In 17-month-old rats, spleen cell Con A-induced proliferation and IL-2 production were reduced 5 days after sympathectomy in the absence of changes in CD5+ T cells or IFN-gamma production. Desipramine pretreatment, to block 6-OHDA uptake and prevent sympathectomy, completely blocked the 6-OHDA-induced effects, demonstrating that the destruction of NA nerve fibers is required. After day 5 post-sympathectomy, no sympathectomy-induced alterations in Con A-induced T cell functions were observed in old animals. These differences between young and old rats demonstrate that old animals are more susceptible to loss of sympathetic NA innervation, perhaps because compensatory mechanisms are limited. The sympathectomy-induced reduction in T cell proliferation indicates that splenic NA innervation in old animals, though diminished, can exert a positive regulatory influence on T lymphocyte function. Further study of sympathetic neural-immune interactions in the aged rat may provide a means to improve T cell responsiveness in aging.

Stat6 signaling promotes protective immunity against Trichinella spiralis through a mast cell- and T cell-dependent mechanism.

Studies in mice infected with the gastrointestinal nematode parasite Nippostrongylus brasiliensis demonstrated that IL-4/IL-13 activation of Stat6 suppresses development of intestinal mastocytosis and does not contribute to IL-4/IL-13 production, but is still essential for parasite expulsion. Because expulsion of another gastrointestinal nematode, Trichinella spiralis, unlike N. brasiliensis expulsion, is mast cell dependent, these observations suggested that T. spiralis expulsion would be Stat6 independent. Instead, we find that Stat6 activation by IL-4/IL-13 is required in T. spiralis-infected mice for the mast cell responses that induce worm expulsion and for the cytokine responses that induce intestinal mastocytosis. Furthermore, although IL-4 induces N. brasiliensis expulsion in the absence of B cells, T cells, and mast cells, mast cells and T cells are required for IL-4 induction of T. spiralis expulsion. Thus, Stat6 signaling is required for host protection against N. brasiliensis and T. spiralis but contributes to expulsion of these two worms by different mechanisms. The induction of multiple effector mechanisms by Stat6 signaling provides a way for a cytokine response induced by most gastrointestinal nematode parasites to protect against most of these parasites, even though different effector mechanisms are required for protection against different nematodes.