Functional homology of tachykinin signalling: The influence of human substance P on the immune system of the mealworm beetle, Tenebrio molitor L.

Tachykinin-related peptides (TRPs) are one of the most prominent families of neuropeptides in the animal kingdom. Insect TRPs display strong structural and functional homology to vertebrate tachykinins (TKs). To study functional homologies between these two neuropeptide families, the influence of human substance P (SP, one of the essential vertebrate TKs) on the immune system of the mealworm beetle, Tenebrio molitor L., was analysed. Human SP influences the phagocytic abilities of T. molitor haemocytes. Peptide injection leads to an increase in the number of haemocytes participating in the phagocytosis of latex beads. In contrast, incubation of haemocytes from non-injected beetles in a solution of physiological saline and SP causes a decrease in phagocytic activity. Treatment with human SP also led to increased adhesion of haemocytes, but no changes in the arrangement of the F-actin cytoskeleton were observed. Interestingly, 6 h after human SP injection, increased DNA integrity in T. molitor haemocytes was reported. The opposite effects were observed 24 h after SP injection. Human SP caused the upregulation of humoral immune responses, such as phenoloxidase (PO) activity in the T. molitor haemolymph, and the downregulation of immune-related genes encoding coleoptericin A, tenecin 3 and Toll receptor. However, genes encoding attacin 2 and cecropin were upregulated. Despite these differences, the antimicrobial activity of T. molitor haemolymph was significantly lower in beetles injected with SP than in control beetles. Moreover, an analysis of the direct influence of SP on lysozyme activity was performed. Our results suggest that SP at a concentration of 10-6 M can directly inhibit lysozyme activity. However, an opposite effect was reported after the application of SP at a concentration of 10-4 M. The presented results suggest structural and functional homology between TK signalling in vertebrates and insects. Primarily, this was visible in the context of the humoral response and general antimicrobial activity of T. molitor haemolymph. However, some of the results related to haemocyte function may also indicate the importance of the TK and TRP sequences for evoking immunological effects.

Introduction of laparoscopic nephrectomy for autosomal dominant polycystic kidney disease as the standard procedure.

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder and accounts for 5-10% of all cases of kidney failure. 50% of ADPKD patients reach kidney failure by the age of 58 years requiring dialysis or transplantation. Nephrectomy is performed in up to 20% of patients due to compressive symptoms, renal-related complications or in preparation for kidney transplantation. However, due to the large kidney size in ADPKD, nephrectomy can come with a considerable burden. Here we evaluate our institution's experience of laparoscopic nephrectomy (LN) as an alternative to open nephrectomy (ON) for ADPKD patients. MATERIALS AND METHODS: We report the results of the first 12 consecutive LN for ADPKD from August 2020 to August 2021 in our institution. These results were compared with the 12 most recent performed ON for ADPKD at the same institution (09/2017 to 07/2020). Intra- and postoperative parameters were collected and analyzed. Health related quality of life (HRQoL) was assessed using the SF36 questionnaire. RESULTS: Age, sex, and median preoperative kidney volumes were not significantly different between the two analyzed groups. Intraoperative estimated blood loss was significantly less in the laparoscopic group (33 ml (0-200 ml)) in comparison to the open group (186 ml (0-800 ml)) and postoperative need for blood transfusion was significantly reduced in the laparoscopic group (p = 0.0462). Operative time was significantly longer if LN was performed (158 min (85-227 min)) compared to the open procedure (107 min (56-174 min)) (p = 0.0079). In both groups one postoperative complication Clavien Dindo ≥ 3 occurred with the need of revision surgery. SF36 HRQol questionnaire revealed excellent postoperative quality of life after LN. CONCLUSION: LN in ADPKD patients is a safe and effective operative procedure independent of kidney size with excellent postoperative outcomes and benefits of minimally invasive surgery. Compared with the open procedure patients profit from significantly less need for transfusion with comparable postoperative complication rates. However significant longer operation times need to be taken in account.

Operating room time savings in Germany- and UK-based hospitals with 3D- VS. 2D-imaging technology in laparoscopic surgery: Meta analysis and budget impact model - Health economic evaluation.

AIMS: Opportunity cost (OC) analysis is key when evaluating surgical techniques. Operating room (OR) time is one potential source of OC in laparoscopic surgery. This study quantifies differences in OR time between 3D- and 2D-imaging technology in laparoscopic surgery, translates these into OC and models the economic impact in real-world hospitals. METHODS: First a systematically performed literature review and meta-analysis were conducted. Then, methods to translate OR time savings into OC were theorised and a budget impact model was created. After that, the potential time savings of real-world hospital case mixes were extrapolated. Finally, the opportunity costs of not using 3D-imaging in laparoscopic surgery were evaluated. RESULTS: Average OR time saving per laparoscopic procedure was -19.4 min (-24.3; -14.5) (-14%) in favour of 3D. The Budget Impact Model demonstrated an economic impact of using 3D-laparoscopy instead of 2D laparoscopy, ranging from £183,045-£866,316 in the British and 73,049€-437,829€ in German hospitals, modelling a mixture of cost savings and performing additional procedures (earning additional revenue). CONCLUSION: The OC analysis revealed significant economic benefits of introducing 3D-imaging technology in laparoscopic surgery, on the basis that average procedure time is reduced. Utilising the saved OR time to perform additional procedures was the biggest driver of OC. Hospital case mix and procedure volume indicated the magnitude of the OC.

A possible role of tachykinin-related peptide on an immune system activity of mealworm beetle, Tenebrio molitor L.

Tachykinin-related peptides (TRPs) are important neuropeptides. Here we show that they affect the insect immune system, especially the cellular response. We also identify and predict the sequence and structure of the tachykinin-related peptide receptor (TRPR) and confirm the presence of expression of gene encoding TRPR on Tenebrio molitor haemocytes. After application of the Tenmo-TRP-7 in T. molitor the number of circulating haemocytes increased and the number of haemocytes participating in phagocytosis of latex beads decreased in a dose- and time-dependent fashion. Also, Tenmo-TRP-7 affects the adhesion ability of haemocytes. Six hours after injection of Tenmo-TRP-7, a decrease of haemocyte surface area was observed under both tested Tenmo-TRP-7 concentrations (10-7 and 10-5 M). The opposite effect was reported 24 h after injection, which indicates that the influence of Tenmo-TRP-7 on modulation of haemocyte behaviour differs at different stages of stress response. Tenmo-TRP-7 application also resulted in increased phenoloxidase activity 6 and 24 h after injection. The assessment of DNA integrity of haemocytes showed that the injection of Tenmo-TRP-7 at 10-7 M led to a decrease in DNA damage compared to control individuals. This effect was only visible 6 h after Tenmo-TRP-7 application. After 24 h, Tenmo-TRP-7 injection increased DNA damage. We also confirmed the expression of immune-related genes in nervous tissue of T. molitor. Transcripts for genes encoding receptors participating in pathogen recognition processes and antimicrobial peptides were detected in T. molitor brain, retrocerebral complex and ventral nerve cord. These results may indicate a role of the insect nervous system in pathogen recognition and modulation of immune response similar to vertebrates. Taken together, our results support the notion that tachykinin-related peptides probably play an important role in the regulation of the insect immune system. Moreover, some resemblances with action of tachykinin-related peptides and substance P showed that insects can be potential model organisms for analysis of hormonal regulation of conserved innate immune mechanisms.

Autocrine growth limitation of human papillomavirus type 16-harboring keratinocytes by constitutively released tumor necrosis factor-alpha.

TNF-alpha is known to exert antitumor and antiviral effects and to participate in the regulation of the immune response. In our study we demonstrate that human rTNF-alpha specifically blocks growth of SK-v keratinocyte cell line harboring and expressing human papillomavirus type 16 (HPV16) sequences. This inhibitory effect was shown by [3H]TdR incorporation and cell counting. Binding experiments with 125I-TNF-alpha showed that SK-v cells express about 10,000 single class TNF-alpha R per cell with affinity constant of about 0.7 nM. Binding of 125I-TNF-alpha could be inhibited by htr-9 mAb recognizing a 55/60-kDa type I TNF-alpha R but not by utr-1 mAb recognizing 75/80-kDa type II TNF-alpha R or irrelevant mAb specific for HPV16E7 protein. Addition of anti-TNF-alpha antibodies to SK-v cell culture resulted in significant (p < 0.05), dose-dependent stimulation of their proliferation. SK-v cells constitutively expressed TNF-alpha mRNA, and SK-v CM contained TNF-alpha, as demonstrated by Northern blot analysis, a specific ELISA, Western blot analysis, and a bioassay with TNF-alpha-sensitive L-M cells. HPLC gel filtration of SK-v cell CM showed that the factor cytotoxic for L-M cells coeluted with immunoreactive TNF-alpha. These results demonstrate that HPV16-harboring SK-v cells constitutively express and release immunoreactive and biologically active TNF-alpha that in turn may exert an autocrine growth inhibitory effect. This phenomenon could represent one of the self-limiting mechanisms controling growth of HPV-induced neoplasia.

Production of natural killer cell activity-augmenting factor (interleukin-6) by human epiphyseal chondrocytes.

OBJECTIVE: We sought to determine the capacity of human epiphyseal chondrocytes to modulate the cytotoxic activity of human natural killer (NK) cells by determining whether they release interleukin-6 (IL-6), a cytokine recently shown to stimulate NK cell activity. METHODS: Conditioned medium from human epiphyseal chondrocyte cultures (Ch-CM) was tested for IL-6 activity using the B9 cell hybridoma assay. Its NK cell-stimulating capacity in the presence of K562 (myelogenous leukemia) cells or human chondrocytes was evaluated in a 4-hour 51Cr-release assay. Ch-CM-derived IL-6/NK cell-augmenting factor activity was partially purified by high-performance liquid chromatography (HPLC) gel filtration and Western blot. RESULTS: Ch-CM contained an NK cell-augmenting factor (NKAF) which was blocked by IL-2 or IL-6 antibodies. Ch-CM did not contain detectable IL-2 activity, but it stimulated IL-2 production by human peripheral blood lymphocytes (PBL). This IL-2-inducing capacity was inhibited by IL-6 antibodies, indicating that chondrocytes release an IL-6-like activity. Ch-CM significantly enhanced the proliferation of IL-6-dependent B9 hybridoma cells, and Western blot analysis of Ch-CM revealed specific bands corresponding to those of highly purified IL-6. Upon HPLC gel filtration, chondrocyte NKAF copurified with chondrocyte IL-6. Pure IL-6 and chondrocyte IL-6 were tested for their ability to stimulate the cytotoxic activity of human PBL against chondrocytes. Both mediators significantly enhanced chondrocyte killing. Lysis of chondrocytes by PBL was mediated by NK cells, since depletion of CD16+ cells resulted in inhibition of the activity. CONCLUSION: Thus, upon stimulation, chondrocytes produce IL-6 which, through IL-2 induction, augments the activity of NK cells against K562 target cells as well as against chondrocytes.

Treatment of systemic sclerosis with gamma-interferon.

Numerous drugs have been recommended for the treatment of systemic sclerosis, but without any significant effect on the fibrotic stage of this disorder. Because recombinant gamma-interferon (gamma-IFN) is a potent and selective inhibitor of fibroblast proliferation and collagen production by human dermal fibroblasts in vitro, we assessed the effects of gamma-IFN treatment on the skin and on pulmonary function in patients with systemic sclerosis. Fourteen patients entered the study, and nine completed the 12-month trial. Fifty micrograms/day of gamma-IFN was administered subcutaneously 3 days per week. At the end of the 12-month treatment period a significant improvement was observed in total skin score, and blood gas analysis showed a significant increase in Pa O2 during therapy with gamma-interferon. Other clinical parameters (dysphagia, Raynaud's phenomenon, cardiac involvement) were not altered significantly. No serious adverse effects were noted. These results suggest a beneficial effect of gamma-IFN on the cutaneous fibrotic abnormalities and on lung fibrosis in systemic sclerosis.

Modulation of intercellular adhesion molecule-1 expression on human melanocytes and melanoma cells: evidence for a regulatory role of IL-6, IL-7, TNF beta, and UVB light.

Intercellular adhesion molecule-1 (ICAM-1) is involved in cell-cell interactions of leukocytes and parenchymal cells and thus plays an important role in immunologic and inflammatory reactions. The expression of ICAM-1 that is found on many different cells such as melanocytes and melanoma cells is induced by various cytokines, including interferon-gamma (IFN gamma), interleukin (IL)-1 and tumor necrosis factor alpha (TNF alpha). Because expression of ICAM-1 in melanoma was found to correlate with increased risk of metastasis, the regulation of ICAM-1 expression on human melanocytes and melanoma cells was investigated. Foreskin-derived melanocytes and melanoma cell lines (A375, G361) were incubated with different cytokines and ICAM-1 expression was evaluated by fluorescence-activated cell sorter. IFN gamma, IL-1, IL-7, TNF alpha, and TNF beta significantly upregulated ICAM-1 expression in a dose-dependent manner. Most interestingly, the cytokine IL-6, which does not influence adhesion-molecule expression on other cells, significantly upregulated melanocyte and melanoma cell ICAM-1 expression. This effect was dose dependent and could be blocked by an IL-6 antibody. Irradiation with ultraviolet (UVB) light did not influence constitutive ICAM-1 expression on melanoma cells and melanocytes, but suppressed cytokine-induced ICAM-1 expression when cells were harvested 16 h after irradiation. These findings were further confirmed by Northern blot analysis, showing a marked accumulation of ICAM-1 mRNA after cytokine treatment, which was reduced by irradiation with UVB light. However, when UVB-exposed melanoma cells were cultured for at least 48 h induction of ICAM-1 expression was observed. These data indicate that, similar to other cells, ICAM-1 expression on melanoma cells and melanocytes is regulated by cytokines and that UVB light affects ICAM-1 expression on melanocytic cells in a biphasic manner.

Interleukin-6 expression by fibroblasts grown in three-dimensional gel cultures.

We investigated the expression and biological activity of interleukin-6 (IL-6) by human fibroblasts cultured as monolayers and within three-dimensional type I collagen lattices. In the course of contracting the gel to a dense tissue-like structure, the cells upregulated their levels of IL-6 mRNA as well as IL-6 biological activity. While there was little mRNA and protein activity (6,500 U/ml) in monolayer cultures, fibroblasts in the 3D system showed a 13-fold increase in IL-6 mRNA on day 3. IL-6 protein was increased 6-fold (38,000 U/ml) on day 4. Stimulation of fibroblast cultures with IL-1 alpha resulted in enhanced IL-6 production in both systems, but the fibroblasts embedded into the 3D network continued to exhibit higher levels.

Hexagonal surface gradient coil for localized MRS of the heart.

A surface gradient coil designed to obtain localized magnetic resonance spectroscopy of the heart in vivo is described. Images and 31P spectra from phantoms and both pig and dog hearts in vivo are shown. The coil was used in conjunction with a rf surface coil to obtain 31P spectra from transmural sections of the left ventricular wall of a dog heart in vivo to demonstrate differences between normal and ischemic tissue.

Constitutive release of IL6 by human papillomavirus type 16 (HPV16)-harboring keratinocytes: a mechanism augmenting the NK-cell-mediated lysis of HPV-bearing neoplastic cells.

In the present study we demonstrate that the cultured human keratinocyte cell line (SK-v cells) harboring and expressing integrated human papillomavirus type 16 (HPV16) DNA sequences constitutively releases IL6, which is known as a pleiotropic immunoregulatory cytokine of potential antitumor properties. The presence of IL6 activity in SK-v cell-conditioned media (SK-v CM) was demonstrated by tritiated thymidine incorporation into IL6-dependent B9 murine plasmacytoma cells. The effect on B9 cells was specific since it could be inhibited by anti-IL6 neutralizing antibodies but not by a normal control serum. IL6 did not affect SK-v cell growth; however, it significantly augmented NK cell activity of human peripheral blood lymphocytes against both K562 erytholeukemic and SK-v cells as assessed by 51Cr release assay. SK-v CM displayed NK cell-augmenting activity that copurified with IL6 activity in both size exclusion and anion-exchange HPLC. Furthermore, SK-v cell-derived NK cell stimulatory activity could be neutralized with anti-IL6 antibodies. These results suggest that HPV-harboring neoplastic cells can release IL6 which may indirectly mediate tumor death by augmentation of NK cell activity.

Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis.

Interleukin-6 (IL-6) is a multifunctional inflammatory cytokine that is produced by monocytes and keratinocytes upon stimulation. Because psoriasis is a skin disease characterized by a hyperproliferative activity of keratinocytes and an inflammatory infiltrate, in the present study IL-6 production of monocytes and keratinocytes of patients with psoriasis was investigated. Peripheral blood mononuclear cells (PBMC) derived from psoriatics, atopics, and healthy controls were incubated for 24 h and, subsequently, supernatant IL-6 activity was measured using an IL-6-dependent hybridoma cell line (B9). Compared to controls and atopics, PBMC of psoriatics produced significantly increased amounts of biologically active IL-6. These findings were also confirmed by Western blot analysis using a specific antiserum directed against IL-6. Moreover, when the sera of the same patients were tested for IL-6 activity, sera of psoriatics contained significantly elevated amounts of circulating IL-6 in comparison to samples from atopics and healthy controls. In contrast to normal or uninvolved skin, keratinocytes in psoriatic lesions were remarkably positive for IL-6 as detected by immunohistochemistry and in situ hybridization. In addition, IL-6 also was found to induce its own synthesis and release by monocytes. These findings indicate that keratinocytes and monocytes in psoriasis are activated to produce increased amounts of IL-6, which may be one of the mediators involved in the regulation of both local and systemic inflammatory reactions occurring in skin diseases such as psoriasis.

Regulation of epidermal cell interleukin-6 production by UV light and corticosteroids.

Epidermal cells (EC) are well known as a source of cytokines, including interleukin (IL)-6. In the present study, we investigated whether ultraviolet (UV) light and corticosteroids (CS) affect IL-6 production by normal (HNK) or malignant (KB) human keratinocytes. Supernatants derived from UVB (100 J/m2)- but not from UVA (100-1500 kJ/m2)-exposed EC (HNK and KB) contained significantly increased levels of IL-6 activity. This was also confirmed by Western blot analysis, resulting in specific bands at 23 kD and 27 kD. Northern blot analysis revealed an enhanced IL-6 mRNA expression after UVB exposure. Addition of hydrocortisone, prednisolone, or dexamethasone immediately after UVB irradiation significantly blocked UVB or IL-1-induced IL-6 mRNA expression and production by EC. The suppressive effect was observed at doses in the physiologic (10(-7)-10(-9) M) as well as pharmacologic (10(-5)-10(-7) M) range. In contrast, the nonactive steroid prednisone did not affect EC IL-6 mRNA expression. These findings indicate that increased IL-6 production by EC after UVB irradiation may mediate local and systemic inflammatory reactions following extensive sun exposure. Thus, the therapeutic effect of corticosteroids observed in various inflammatory diseases may be partly due to their downregulating capacity of IL-6 production.

Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light.

Tumor necrosis factor alpha (TNF-alpha), in addition to being cytotoxic for certain tumor cells, has turned out as a multifunctional cytokine that is involved in the regulation of immunity and inflammation. Since human keratinocytes have been demonstrated to be a potent source of various cytokines, it was investigated whether epidermal cells synthesize and release TNF-alpha. Supernatants derived from normal human keratinocytes (HNK) and human epidermoid carcinoma cell lines (KB, A431) were tested both in a TNF-alpha-specific ELISA and a bioassay. In supernatants of untreated epidermal cells, no or minimal TNF-alpha activity was found, while after stimulation with lipopolysaccharide (LPS) or ultraviolet (UV) light, significant amounts were detected. Western blot analysis using an antibody directed against human TNF-alpha revealed a molecular mass of 17 kD for keratinocyte-derived TNF-alpha. These biological and biochemical data were also confirmed by Northern blot analysis revealing mRNA specific for TNF-alpha in LPS- or ultraviolet B (UVB)-treated HNK and KB cells. In addition, increased TNF-alpha levels were detected in the serum obtained from human volunteers 12 and 24 h after a single total body UVB exposure, which caused a severe sunburn reaction. These findings indicate that keratinocytes upon stimulation are able to synthesize and release TNF-alpha, which may gain access to the circulation. Thus, TNF-alpha in concert with other epidermal cell-derived cytokines may mediate local and systemic inflammatory reactions during host defense against injurious events caused by microbial agents or UV irradiation.

[Studies on the production of epidermal cytokines after UVB irradiation in patients with epidermodysplasia verruciformis]. / Badania nad produkcja cytokin naskórkowych pod wplywem UVB u chorych z epidermodysplasia verruciformis.

The production of interleukin-1 (IL-1) and interleukin-1 inhibitor by keratinocytes isolated from the skin of epidermodysplasia verruciformis patients was studied. Keratinocytes from uninvolved skin of patients with most pronounced neoplastic lesions produced large amounts of an IL-1 inhibitor (20-40 kD). Keratinocytes from preneoplastic lesions showed no significant differences compared to cells from healthy donors but their production of IL-1 after UVB irradiation was increased.

Epidermal cell-contra-interleukin 1 inhibits human accessory cell function by specifically blocking interleukin 1 activity.

Ultraviolet B (UVB) radiation (280-320 nm) is capable of suppressing selected cell mediated immune responses by inhibiting the function of antigen presenting/accessory cells. Human keratinocytes and carcinoma cell lines (A431) upon UVB radiation or treatment with PMA secrete a suppressor factor, which blocks IL 1 activity (hEC-contra-IL 1). Therefore, the capacity of this UVB-inducible cytokine to modulate human accessory cell function was tested. Human peripheral blood mononuclear cells were stimulated with the mitogenic anti-CD3 monoclonal antibody OKT3 and thymidine incorporation into proliferating T-cells was measured as an index for monocyte accessory cell activity. Addition of hEC-contra-IL 1 which was purified by HPLC chromatography partially decreased OKT3 induced T-cell proliferation in a dose dependent manner. Human EC-contra-IL 1, however, failed to inhibit blastogenesis when T-cells depleted of accessory cells were stimulated in an accessory cell independent fashion via OKT3 attached to the bottom of microtiter plates. Recombinant human (rh) IL 1, but not rhIL 6 was able to reconstitute hEC-contra-IL 1 suppressed blastogenesis in a dose dependent manner. Furthermore, the combined addition of h-EC-contra-IL 1 and an antibody against rhIL 6 to cultures resulted in an additive inhibitory effect which could not be observed when hEC-contra-IL 1 was added together with a monoclonal antibody against rhIL 1 alpha/beta. These studies indicate that hEC-contra-IL 1 is capable of suppressing human accessory cell function by specifically blocking IL 1 activity. This property of hEC-contra-IL 1 points to a novel mechanism by which UVB radiation may modulate human accessory cell function in an indirect manner.

Binding of recombinant interleukin-1 beta to the third complement component and alpha 2-macroglobulin after activation of serum by immune complexes.

Activation of human normal serum with tetanus/antitetanus immune complexes (TAT-IC) resulted in increased binding of 125I-labeled interleukin-1 beta (IL-1 beta) to serum factors, as opposed to untreated serum. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by autoradiography showed labeling of two large molecular mass factors of an apparent molecular weight (Mr) of 200,000 and 400,000, respectively. These complexes could be dissociated by reduction. No complexes were formed when reducing compounds were added to serum-TAT-IC-125I-IL-1 beta mixtures. Complex formation was largely prevented by alkylating compounds. Molecular sieve chromatography of TAT-IC-activated serum confirmed that 125I-IL-1 beta became bound to high Mr serum proteins. Fractions containing high molecular 125I-IL-1 serum protein complexes partially retained IL-1-like activity since they induced proliferation of an IL-1-dependent murine T helper (D10G4) cell lineage. The 125I-IL-1 beta binding factors could be immunoprecipitated from TAT-IC-activated serum 125I-IL-1 beta solutions by antisera to alpha 2-macroglobulin (alpha 2M) or to the third complement component (C3). SDS-PAGE of the immunoprecipitates showed radioactive bands corresponding to the expected Mr resulting from complex formation between 125I-IL-1 beta and these two proteins. Treatment of purified plasma alpha 2M and C3 with trypsin or activation with methylamine, which causes cleavage of the internal thiol ester and the appearance of free thiol groups in these proteins, mediated binding of 125I-IL-1 beta to alpha 2M and C3b. The results suggest that cleavage of the internal thiol ester in C3 and alpha 2M makes these plasma proteins susceptible to binding of 125I-IL-1 beta and that free thiol groups do play a role in the formation of 125I-IL-1 beta plasma protein complexes. Activated C3 and alpha 2M may function as IL-1 beta carrier proteins in biologic fluids, in addition to their other physiologic roles.

Ultraviolet light induces increased circulating interleukin-6 in humans.

Although the clinical effects of acute exposure to ultraviolet (UV) light--such as cutaneous inflammation, malaise, somnolence, chills and fever--have been appreciated many years, the underlying mechanisms mediating these effects are poorly understood. Interleukin-6 (IL-6) is a potent cytokine with a wide variety of biologic activities, including induction of fever and acute phase response. Because IL-6 is produced by keratinocytes in vivo and in vitro and because the release is enhanced by UV light, the present study was performed to investigate the effect of a single UV dose eliciting moderate to severe sunburn reaction on the production of IL-6 in vivo. Therefore, plasma of UV-treated human subjects was evaluated for IL-6 activity by testing its capacity to induce the proliferation of an IL-6-dependent hybridoma cell line (B9). In contrast to plasma samples obtained before UV exposure, post-UV-specimens contained significant levels of IL-6 peaking at 12 h after UV irradiation. Plasma IL-6 activity was neutralized by an antiserum directed against recombinant human IL-6, and upon HPLC gel filtration exhibited a molecular weight of around 20 kD. Moreover, plasma IL-6 levels correlated remarkably with fever course followed by an increase of acute phase proteins such as C-reactive protein. These data indicate that IL-6, which is released by keratinocytes following UV exposure, may gain access to the circulation and via its pyrogenic as well as acute phase-inducing effect may function as an important mediator of systemic sunburn reaction.