House dust mite allergens Der f and Der p induce IL-31 production by blood-derived T cells from atopic dermatitis patients.

Aero-allergens, such as house dust mite (HDM), have been suggested to play a role in the initiation of atopic dermatitis (AD)-related skin inflammation. Here, we analysed the proliferation and the cytokine expression of blood-derived T cells from AD and healthy individuals upon HDM-allergen stimulation. The proliferating cells from healthy individuals and AD patients had a significantly different, distinct cytokine profile: in AD blood, we found increased frequencies of HDM-reactive IL-31-producing T cells, as well as a decreased Th1/Th2 and Tc1/Tc2 ratio, suggesting that allergen-specific T cells in blood of chronic AD patients are subject to pre-existent Th2-Tc2 and "Th31-Tc31" programming.

Wet work and hand eczema in apprentice nurses; part I of a prospective cohort study.

BACKGROUND /OBJECTIVES: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. Here, we report an investigation on wet work exposure and its influence on the risk of developing hand eczema in apprentice nurses. METHODS: A prospective cohort study was performed among 721 Dutch apprentice nurses. Participants recorded wet work exposure and symptoms of hand eczema using specially designed diary cards. RESULTS: For 533 apprentice nurses, a follow-up time of 1-3 years was completed. Diary cards were supplied by 383 students. The 1-year period prevalence of hand eczema was 23% in the first year, 25% in the second year and 31% in the third year of follow-up. Eighty-one new cases of hand eczema developed, most of which occurred during the first year of follow-up. In approximately one-third of the participants, wet work exposure exceeded the national guidelines. Frequent hand washing during traineeships [odds ratio (OR) 1.5; 90% confidence interval (CI) 1.0-2.3], frequent hand washing at home (OR 2.3; 90% CI 1.5-3.7) and having a side job involving wet work (OR 1.6; 90% CI 1.0-2.4) were independent risk factors for hand eczema. CONCLUSION: As a considerable number of apprentice nurses had already developed hand eczema during traineeships, more attention should be paid to skin protection in vocational education.

Filaggrin loss-of-function mutations and atopic dermatitis as risk factors for hand eczema in apprentice nurses: part II of a prospective cohort study.

BACKGROUND/OBJECTIVES: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. In this study, we investigated the effect of loss-of-function mutations in the filaggrin gene (FLG), atopic dermatitis and wet work exposure on the development of hand eczema in apprentice nurses. METHODS: Dutch apprentice nurses were genotyped for the four most common FLG mutations; atopic dermatitis and hand eczema history were assessed by questionnaire. Exposure and hand eczema during traineeships were assessed with diary cards. RESULTS: The prevalence of hand eczema during traineeships was higher among subjects with a history of hand eczema reported at inclusion. Hand washing during traineeships and at home increased the risk of hand eczema. After adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5 (90% confidence interval 1.7-3.7) was found for a history of atopic dermatitis. In this study, an increased risk of hand eczema conferred by FLG mutations could not be shown, but subjects with concomitant FLG mutations and atopic dermatitis showed the highest risk of hand eczema during traineeships. CONCLUSION: A history of atopic dermatitis, a history of hand eczema and wet work exposure were the most important factors increasing the risk of hand eczema during traineeships.

Increased frequencies of IL-31-producing T cells are found in chronic atopic dermatitis skin.

Interleukin (IL)-31 has been associated with pruritus, a characteristic feature of atopic dermatitis (AD). Local T cell responses may be responsible for the increased level of IL-31 mRNA observed in AD. We investigated the frequency of IL-31-producing T cells in AD lesions, as well as their cytokine profile. T cells were isolated from chronic AD lesions, autologous blood and healthy donor skin. Intracellular expression of IL-31, IFN-γ, IL-13, IL-17 and IL-22 was measured using flow cytometry. T cells from AD lesions contained significantly higher percentages of IL-31-producing T cells compared to autologous blood and donor skin. Many IL-31-producing T cells co-produced IL-13 and to lesser extent IL-22, but rarely IFN-γ or IL-17. A substantial part of the IL-31-producing T cells did not co-produce any of the other cytokines and could therefore not be linked to any of the known functionally different T cell subsets. The T cell infiltrates were also relatively enriched for Th2/Tc2 and Th22/Tc22 cells, while frequencies of Th1/Tc1 and Th17 cells were decreased. This is the first report describing the detection of IL-31 at protein level in skin-infiltrating T cells. We show here that T cells in chronic AD skin produce IL-31 and that AD lesions contain increased levels of these IL-31-producing T cells. This suggests that a substantial part of previously reported increased IL-31 mRNA levels in AD skin is T cell derived and that these cells may be involved in the pathogenesis of AD.

A prospective, randomized, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: effects of adalimumab treatment on lesional and nonlesional skin.

BACKGROUND: There is a need for biomarkers to screen the effectiveness of (novel) therapeutic agents for psoriasis at an early stage. OBJECTIVE: We aimed to determine which of the changes in psoriatic skin correlates best with clinical improvement 4 weeks after effective adalimumab therapy. METHODS: Twenty-two psoriatic arthritis patients were randomized to receive adalimumab or placebo. T cell numbers and markers of innate immunity were estimated in lesional and nonlesional skin biopsies at baseline and after 4 weeks of treatment. RESULTS: CD161+ and elastase+ dermal cells in lesional skin were significantly reduced upon 4 weeks of successful adalimumab treatment compared with placebo. CONCLUSION: Early improvement of psoriasis lesions during adalimumab therapy is associated with a marked reduction of infiltrated dermal CD161+ T cells and elastase+ neutrophils, suggesting that these parameters could be used as biomarkers to monitor early changes after active treatment in small proof-of-concept studies of short duration.

Formation of fibrosis after nonablative and ablative fractional laser therapy.

BACKGROUND: Fractional laser therapy (FLT) has become a widely accepted modality for skin rejuvenation and has also been used in various other skin diseases. OBJECTIVE: To observe long-term histologic effects of nonablative and ablative FLT in the treatment of pigment disorders. METHODS: A randomized controlled observer-blinded study was performed in 18 patients with pigment disorders. Two similar test regions were randomized to receive FLT with intermittent topical bleaching or topical bleaching alone. Patients with ashy dermatosis (AD) and postinflammatory hyperpigmentation (PIH) were treated using nonablative 1,550-nm FLT (15 mJ/microbeam, 14-20% coverage), whereas patients with Becker's nevus (BN) were treated with ablative 10,600-nm FLT (10 mJ/microbeam, 35-45% coverage) for three to five sessions. Biopsies were obtained 3 months after the last treatment. RESULTS: At follow-up, dermal fibrosis was observed in four of eight patients treated using ablative FLT and no patients treated using nonablative FLT (p < .05). CONCLUSIONS: Assuming that the dermal response is comparable in AD, PIH, and BN, at the given settings, ablative FLT may induce fibrosis, whereas treatment with nonablative FLT does not. Whether formation of fibrosis has to be regarded as dermal remodeling or a subtle subclinical form of scarring should be investigated in future research.

Ablative fractional laser therapy as treatment for Becker nevus: a randomized controlled pilot study.

BACKGROUND: Becker nevus (BN) is an uncommon pigment disorder characterized by hyperpigmentation and sometimes hypertrichosis. To date, no effective treatment has been available. OBJECTIVES: We sought to assess efficacy and safety of ablative 10,600-nm fractional laser therapy (FLT) in the treatment of BN. METHODS: Eleven patients with BN, older than 18 years, were included in a prospective randomized controlled, observer-blinded split-lesion trial. In each patient two similar square test regions were randomized to either ablative FLT at 10 mJ/microbeam, coverage 35% to 45%, and topical bleaching (to prevent laser-induced postinflammatory hyperpigmentation), or topical bleaching alone (to allow comparison of the regions). At 3- and 6-month follow-up, clearance of hyperpigmentation was assessed by physician global assessment, reflectance spectroscopy, melanin index, patient global assessment, patient satisfaction, and histology. RESULTS: At 6-month follow-up, physician global assessment improved in the FLT region (P < .05). Reflectance spectroscopy, melanin index, number of melanocytes, and amount of dermal melanin did not significantly differ between the regions. Patient global assessment and patient satisfaction were 5.0 and 5.9 (visual analog scale score, 0-10), respectively. Side effects were postinflammatory hyperpigmentation (n = 3), erythema (n = 3), burning sensation (n = 3), crusting (n = 3), edema (n = 2), and blistering (n = 2). LIMITATIONS: Limitations include the small number of patients, treatment in spring, possibly suboptimal laser settings, and the combined usage of FLT and a bleaching agent. CONCLUSION: Ablative FLT was moderately effective in some patients with BN. However, postinflammatory hyperpigmentation and relatively negative patient-reported outcomes still preclude ablative FLT from being a standard therapy. Larger studies with different laser settings will be required to optimize this treatment modality.

Nonablative 1550-nm fractional laser therapy versus triple topical therapy for the treatment of melasma: a randomized controlled pilot study.

BACKGROUND: Various treatments are currently available for melasma. However, results are often disappointing. OBJECTIVE: We sought to assess the efficacy and safety of nonablative 1550-nm fractional laser therapy and compare results with those obtained with triple topical therapy (the gold standard). METHODS: Twenty female patients with moderate to severe melasma and Fitzpatrick skin types II to V were treated either with nonablative fractional laser therapy or triple topical therapy (hydroquinone 5%, tretinoin 0.05%, and triamcinolone acetonide 0.1% cream) once daily for 8 weeks in a randomized controlled observer-blinded study. Laser treatment was performed every 2 weeks for a total of 4 times. Physician Global Assessment was assessed at 3 weeks, 3 months, and 6 months after the last treatment. RESULTS: Physician Global Assessment improved (P < .001) in both groups at 3 weeks. There was no difference in Physician Global Assessment between the two groups. Mean treatment satisfaction and recommendation were significantly higher in the laser group at 3 weeks (P < .05). However, melasma recurred in 5 patients in both groups after 6 months. Side effects in the laser group were erythema, burning sensation, facial edema, and pain; in the triple group side effects were erythema, burning, and scaling. LIMITATIONS: Limitations were: small number of patients; only one set of laser parameters; and a possible difference in motivation between groups. CONCLUSIONS: Nonablative fractional laser therapy is safe and comparable in efficacy and recurrence rate with triple topical therapy. It may be a useful alternative treatment option for melasma when topical bleaching is ineffective or not tolerated. Different laser settings and long-term maintenance treatment should be tested in future studies.

Reduction of different inflammatory cell types of the innate immune system in psoriatic skin during etanercept treatment.

To investigate whether specific markers for innate immunity would diminish with successful treatment in psoriasis, we analyzed lesional and non-lesional skin biopsies taken from patients with moderate to severe psoriasis during 12 weeks of treatment with etanercept in correlation with the clinical response. In the clinical responders (PASI reduction >50%), all markers (CD3, CD68, CD161, elastase, BDCA-2, TNF-alpha) showed a decline during treatment, indicating a pivotal role for innate immunity in the pathogenesis of psoriasis.

Atopic eczema or atopiform dermatitis.

Age period prevalence of atopic eczema (AE), a very common skin disease, has increased during the past decennia. This expansion seems to be ending in wealthy countries, while an increase is observed in developing nations, for which there is no firm explanation. Recent steps in understanding AE are the detection of skin barrier related filaggrin null mutations in approximately 25% of patients and the recognition of IL-31 as a molecule possibly involved in the itch (pruritus). Also interesting are the recognition of thymus and activation-regulated chemokine (TARC) and proliferating-inducing ligand (APRIL), as being associated with AE severity and activity. Immunocentric and corneocentric views on pathogenesis (the inside-outside paradigm) and the diagnostic entity atopiform dermatitis (AFD) are discussed here. We emphasize that diagnosing AE is not simple but challenging. We accentuate that a diagnosis of AE is only possible when there is allergen-specific IgE. Advice as to the need for elimination of allergens and adjustment of lifestyle are only proficient in patients having atopy and true AE, not in those having AFD.

Non-ablative 1,550 nm fractional laser therapy versus triple topical therapy for the treatment of melasma: a randomized controlled split-face study.

BACKGROUND: Melasma is a uichronic, often relapsing skin disorder, with poor long-term results from all current therapies. OBJECTIVE: To assess efficacy and safety of non-ablative 1,550 nm fractional laser therapy (FLT) as compared to the gold standard, triple topical therapy (TTT). STUDY DESIGN: Twenty-nine patients with melasma were included in a randomized controlled observer-blinded study with split-face design. Each side of the face was randomly allocated to either 4-5 non-ablative FLT sessions (15 mJ/microbeam, 14-20% coverage) or TTT (hydroquinone 5%, tretinoin 0.05%, triamcinolone acetonide 0.1% cream). TTT was applied once daily for 15 weeks until the last FLT session. After this last treatment, patients were asked to apply TTT twice weekly on both sides of the face during follow-up. Improvement of melasma was assessed by patient's global assessment (PGA), patient's satisfaction, physician's global assessment (PhGA), melanin index, and lightness (L-value) at 3 weeks, and at 3 and 6 months after the last treatment. RESULTS: Mean PGA and satisfaction were significantly lower at the FLT side (P<0.001). PhGA, melanin index, and L-value showed a significant worsening of hyperpigmentation at the FLT side. At the TTT side, no significant change was observed. At 6 months follow-up, most patients preferred TTT. Side effects of FLT were erythema, burning sensation, edema, and pain. Nine patients (31%) developed PIH after two or more laser sessions. Side effects of TTT were erythema, burning sensation, and scaling. CONCLUSIONS: Given the high rate of postinflammatory hyperpigmentation, non-ablative 1,550 nm fractional laser at 15 mJ/microbeam is not recommendable in the treatment of melasma. TTT remains the gold standard treatment.

Tertiary teledermatology: a systematic review.

Telemedicine is becoming widely used in healthcare. Dermatology, because of its visual character, is especially suitable for telemedicine applications. Most common is teledermatology between general practitioners and dermatologists (secondary teledermatology). Another form of the teledermatology process is communication among dermatologists (tertiary teledermatology). The objective of this systematic review is to give an overview of studies on tertiary teledermatology with emphasis on the categories of use. A systematic literature search on tertiary teledermatology studies used all databases of the Cochrane Library, MEDLINE (1966-November 2007) and EMBASE (1980-November 2007). Categories of use were identified for all included articles and the modalities of tertiary teledermatology were extracted, together with technology, the setting the outcome measures, and their results. The search resulted in 1,377 publications, of which 11 were included. Four categories of use were found: getting an expert opinion from a specialized, often academic dermatologist (6/11); resident training (2/11); continuing medical education (4/11); and second opinion from a nonspecialized dermatologist (2/11). Three modalities were found: a teledermatology consultation application (7/11), a Web site (2/11), and an e-mail list (1/11). The majority (7/11) used store-and-forward, and 3/11 used store-and-forward and real-time. Outcome measures mentioned were learning effect (6), costs (5), diagnostic accuracy (1), validity (2) and reliability (2), patient and physician satisfaction (1), and efficiency improvement (3). Tertiary teledermatology's main category of use is getting an expert opinion from a specialized, often academic dermatologist. Tertiary teledermatology research is still in early development. Future research should focus on identifying the scale of tertiary teledermatology and on what modality of teledermatology is most suited for what purpose in communication among dermatologists.

Postelicitation model of allergic contact dermatitis for predicting the efficacy of topical drugs.

To evaluate the anti-inflammatory efficacies of topical drugs, models of contact hypersensitivity (CHS) can be used, but the conventional murine models of CHS need revision in this respect. These models utilize sensitized mice to study suppression of sensitization or elicitation by test compounds. To mimick the events occurring in allergic contact dermatitis (ACD), a modification of the murine model of CHS is needed in a way that a chronic postelicitation phase of CHS is maintained for studies of anti-inflammatory effects of topical drugs, typically relevant for ACD therapy, not for ACD prevention. A method for the quantification of the suppression of ACD by a test compound is presented here. Two experimental drugs for topical use, imidazole-4-carboxylate and imidazole-4-acetate, were tested in parallel with the corticosteroid prednisolone. We found that prednisolone showed strong suppressive effects, while imidazole-4-carboxylate and imidazole-4-acetate showed mild suppressive effects during persistent ACD simulation. Multiple elicitations on the mouse ears led to scratching and the formation of abrasions and scabbings with, presumably, worsening of discomfort. Clear reduction of these side-phenomena was achieved by tailoring the topical amount of contact sensitizer, while the ability of the ACD model to test anti-inflammatory compounds, was not affected. By focussing on a prolonged postelicitation phase of CHS, a simulation of ACD has been established. We demonstrated that this model may provide an improved predictability for the clinical efficacies of (experimental) mild or strong anti-inflammatory drugs.

The burden of vitiligo: patient characteristics associated with quality of life.

BACKGROUND: Vitiligo is commonly regarded as a harmless cosmetic skin problem in Western societies, and the importance of treating patients with vitiligo is often underestimated. OBJECTIVE: We sought to determine the clinical and sociodemographic variables that adversely affect the quality of life in adult patients with generalized vitiligo so that these variables can be considered in the treatment and care. METHODS: A total of 245 adult patients with generalized vitiligo completed two quality-of-life questionnaires (the Medical Outcomes Study 36-Item Short-form General Health Survey and the Skindex-29). Physicians assessed sociodemographic and clinical characteristics of these patients. RESULTS: Dark skin type, vitiligo located on the chest, and treatment in the past appeared to have an adverse impact on the psychosocial domains of quality of life. Moreover, itch was reported by 20% of the patients in this study. LIMITATIONS: Psychiatric comorbidity was not evaluated in the analyses. CONCLUSION: Generalized vitiligo is a serious skin disorder with an adverse impact on the emotional state, comparable with that of other major skin diseases.

The course of life of patients with childhood atopic dermatitis.

Atopic dermatitis mainly covers the period of infancy to adulthood, an important period in the development of an individual. The impairment of quality of life and the psychological wellbeing of children with atopic dermatitis have been well documented but so far no data exist about the impact of atopic dermatitis in childhood on fulfilling age-specific developmental tasks and achieving developmental milestones during this period, referred to as the course of life. The aims of this study were to: (i) assess the course of life and define the disease-related consequences in young adult patients with childhood atopic dermatitis and (ii) determine whether the severity of atopic dermatitis is predictive for the course of life, the disease-related consequences and quality of life later in life. Adult patients who grew up with atopic dermatitis were asked to complete a medical history questionnaire, the Skindex-29, the "course of life" questionnaire and a subjective disease-specific questionnaire. Patients with severe atopic dermatitis in childhood showed a significant delayed social development in their course of life. The results of the disease-specific questionnaire demonstrated remarkable high percentages of psycho-social consequences and physical discomfort caused by atopic dermatitis in childhood. Patients showed a severely negative impact of atopic dermatitis on their current quality of life. This is the first study that applied the "course of life" questionnaire in atopic dermatitis. More insight in the course of life, disease-specific consequences and quality of life of atopic dermatitis is of high importance, especially in case of severe atopic dermatitis.

Aberrant function of peripheral blood myeloid and plasmacytoid dendritic cells in atopic dermatitis patients.

BACKGROUND: Dendritic cells (DCs) can act both as innate cells in host defense and as antigen-presenting cells for naive T cells in adaptive immunity. These functions, among others, are determined by the level of production of particular cytokines. Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by an initial phase predominated by T(H)2 cytokines that switches into a second, more chronic T(H)1-dominated eczematous phase. OBJECTIVE: To assess to what extent the AD phenotype is associated with an aberrant phenotype and function of DCs. METHODS: Classic CD1c(+)/blood DC antigen (BDCA)-1(+) myeloid (m) DCs and CD304(+)/BDCA4(+) plasmacytoid (p) DCs, the natural IFN-producing cells, were isolated from peripheral blood of patients with AD and healthy controls and analyzed for their phenotype and function. RESULTS: Purified CD1c(+)/BDCA1(+) mDCs from patients with AD showed a selective and dramatic reduction of IL-12p70 and TNF-alpha release. IL-12p70 reduction was attributed to a defective expression of both IL-12p35 and IL-12p40 subunits. Accordingly, mature CD1c(+)/BDCA1(+) mDCs from patients with AD induced considerably less IFN-gamma-producing and more IL-4-producing T(H) cells compared with mDCs from healthy controls. In addition, CD304(+)/BDCA4(+) pDCs from patients with AD produced significantly lower levels of IFN-alpha compared with healthy controls. CONCLUSION: Myeloid DCs and pDCs from patients with AD show defective IL-12, TNF-alpha, and IFN-alpha production, which may contribute to increased susceptibility to infection and to the maintenance of the T(H)2 cell-mediated allergic state in patients with AD.

Clinical differences between atopic and atopiform dermatitis.

BACKGROUND: Atopic dermatitis (AD) has been divided into the "extrinsic" and "intrinsic" type, in which "intrinsic AD" is characterized by the absence of allergen-specific IgE. Still, there is no consensus whether this "intrinsic type" of AD, which we denominate as atopiform dermatitis (AFD), is a distinct entity. OBJECTIVE: A case-control study was performed to compare the clinical and diagnostic features of AD and AFD. METHODS: Patients with a clinical diagnosis of AD were selected. Cases did not have demonstrable allergen-specific IgE. Matched control subjects were tested positive for allergen-specific IgE. Patients were evaluated for medical history, quality of life, disease severity, and Hanifin and Rajka, U.K. and Millennium diagnostic criteria. RESULTS: Eight percent (n = 34) of the selected patients had, in fact, AFD. Female predominance, absence of atopic diseases, later onset of disease, and milder disease severity were observed in AFD. A history of atopy, recurrent conjunctivitis, palmar hyperlinearity, keratosis pilaris, pityriasis alba, and hand and/or food eczema were significantly less present in AFD. Dennie-Morgan fold was positively associated with AFD. LIMITATIONS: Not all patients with negative allergen-specific IgE participated and a relatively small number of AFD patients were studied. CONCLUSIONS: In addition to the absence of allergen-specific IgE, our findings support that AFD is an entity distinct from AD. With a distinction shown between AFD and AD, patient groups will be better defined and more homogeneous. Implications of this distinction will be of importance for preventive and therapeutic advice; diagnostic processes; and for future research.

Topical treatments in psoriasis: today and tomorrow.

Topical therapy in psoriasis is of use in mild cases. It is also applied as an adjunct to phototherapy and systemic treatments in moderate to severe cases. Long-established pharmaceuticals such as cignolin, tar preparations, and glucocorticoids are still in use. Newer topical agents such as vitamin A and D derivatives are gradually replacing them. Combining a vitamin D derivative and a strong glucocorticoid now seems to be the most efficient way to treat psoriasis when topical agents are indicated. There is a growing list of "alternative" treatment options, where evidence is generally absent. Rewarding investments should perhaps be directed at intervening with molecules of innate immunity. Superfluous activation of natural immune system cascades is now in view as the major culprit in psoriasis, replacing the T-cell hypothesis of the disease. Agents directed at tumor necrosis factor alpha, Toll-like receptors, and neutrophils may have great impact in future topical therapy of psoriasis. Finally, innovations in the development of more targeted glucocorticoids and vitamin A and D derivatives, where desired effects are better separated from undesired side effects, may lead to an increased benefit/risk ratio of these nuclear receptor-directed therapies.

Expression of terminal complement components by human keratinocytes.

Human keratinocytes are important constituents of the skin immune system. They produce several cytokines, chemokines as well as some complement proteins. As regards soluble complement proteins, so far keratinocytes have been shown to synthesize only C3, factor B, factor H and factor I. Synthesis and regulation of synthesis of other complement proteins has not yet been studied. Here we studied the synthesis of terminal complement components, C5-C9 by human keratinocytes. We also studied the regulation of terminal complement synthesis in keratinocytes by several cytokines, namely, IL-1alpha, IL-2, IL-6, TGF-beta1, TNF-alpha, and IFN-gamma. Human keratinocytes constitutively expressed C5, C7, C8gamma and C9 mRNA but not C6, C8alpha and C8beta mRNA. They released C7 and C9, but not C5, C6 and C8. None of the cytokines tested had any influence on the synthesis of terminal components except TNF-alpha, which strongly upregulated C9 production. In conclusion, we demonstrate that keratinocytes are capable of synthesizing some of the terminal complement components and that the synthesis of C9 is regulated by TNF-alpha.

Human keratinocytes produce the complement inhibitor factor I: Synthesis is regulated by interferon-gamma.

Extrahepatic complement synthesis is believed to play an important role in host defense and inflammation at tissue and organ level. In the epidermis the most abundant cell type, keratinocytes have been shown to produce C3, factor B and factor H. In the present study, we investigated the synthesis of factor I by human keratinocytes. We also studied whether proinflammatory cytokines IL-1alpha, IL-6, TGF-beta1, TNF-alpha and IFN-gamma regulate factor I synthesis in keratinocytes. Human keratinocytes constitutively expressed factor I mRNA and produced factor I protein. Amongst the above-mentioned cytokines, only IFN-gamma regulated the synthesis of factor I, and this effect occurred predominantly at pre-translational level. Factor I produced by keratinocytes was functionally active in cleaving C3b. In conclusion, we demonstrate that keratinocytes are capable of synthesizing factor I, and that this synthesis is regulated by IFN-gamma.