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Biomedical subjects

U Hofmann

Publications and source records attributed to U Hofmann.

At least 37 records · Page 2Linked to original sources
PubMed2000

In vitro interaction of codeine and diclofenac.

There is very limited knowledge about possible pharmacokinetic interactions between opioid analgesics and nonsteroidal antiinflammatory drugs (NSAIDs), which are commonly used in combination for the treatment of chronic pain. The major metabolic pathway of the weak opioid codeine is glucuronidation to codeine-6-glucuronide. Therefore we investigated the influence of the NSAID diclofenac on the formation of codeine-6-glucuronide in vitro, using human liver tissue homogenate. The formation of codeine-6-glucuronide exhibited single enzyme Michaelis-Menten kinetics with an average V(max) of 93.6 +/- 35.3 pmol/mg/min. A noncompetitive inhibition of codeine-6-glucuronidation by diclofenac was observed with an average K(i) of 7.9 microM. These in vitro findings suggest that a pharmacokinetic interaction occurs in vivo, which has to be confirmed by an interaction study in human subjects. It can be speculated that in case of inhibition of glucuronidation, the amount of codeine available for other pathways especially O-demethylation to morphine is increased, resulting in higher morphine serum levels and therefore higher analgesic efficacy.

Aged↗
PubMed1999

Determination of tetrahydrothiophene formation as a probe of in vitro busulfan metabolism by human glutathione S-transferase A1-1: use of a highly sensitive gas chromatographic-mass spectrometric method.

A method for the sensitive determination of tetrahydrothiophene (THT) in cytosolic incubation mixtures was developed. Busulfan conjugation with glutathione was predominantly catalysed by glutathione S-transferase A1-1 (GST A1-1) and THT was released from the primary metabolite by alkalization. After liquid-liquid extraction using n-pentane separation and quantification of the product was performed by gas chromatography with a mass-selective detector. The method showed good sensitivity, accuracy and reproducibility with a detection limit of 2 ng ml(-1) and a limit of quantification of 5 ng ml(-1). The suitability of the method is shown for enzyme kinetic studies in human liver cytosol as well as for determination of GST A1-1 activity.

Antineoplastic Agents, Alkylating↗
PubMed1999

Highly sensitive gas chromatographic-tandem mass spectrometric method for the determination of morphine and codeine in serum and urine in the femtomolar range.

A sensitive and specific method was developed for the determination of codeine and morphine in human serum and for the determination of trace amounts of endogenous morphine in human urine. The analytes were recovered from serum by a simple liquid-liquid extraction method. Urine samples were hydrolyzed, and purified by two liquid-liquid extraction steps and a solid-phase extraction. Samples were derivatized to the pentafluoropropionic esters and measured by gas chromatography tandem mass spectrometry. Using the deuterated analogues as internal standards a limit of quantification of 20 fmol/ml (5.7 pg/ml) morphine and 500 fmol/ml (150 pg/ml) codeine in human serum and of 2.5 fmol/ml (0.71 pg/ml) morphine in urine was achieved. The method was suitable for the determination of morphine and codeine in pharmacokinetic studies and for the determination of the urinary excretion of endogenous morphine.

Calibration↗
PubMed1999

Rapid, highly sensitive method for the determination of morphine and its metabolites in body fluids by liquid chromatography-mass spectrometry.

A rapid, highly sensitive method for the determination of morphine and its metabolites morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G) and normorphine has been developed using high-performance liquid chromatography-electrospray mass spectrometry, with the deuterated analogues as internal standards. The analytes were extracted automatically using end-capped C2 solid-phase extraction cartridges. Baseline separation of morphine, M3G and M6G was achieved on a LiChrospher 100 RP-18 end-capped analytical column (125x3 mm I.D., 5 microm particle size) with water-acetonitrile-tetrahydrofuran-formic acid (100:1:1:0.1, v/v) as the mobile phase. Morphine and normorphine coeluate and were separated mass spectrometrically. The mass spectrometer was operated in the selected-ion monitoring mode using m/z 272 for normorphine, m/z 286 for morphine, m/z 462 for morphine-6-glucuronide. Due to an interfering peak, M3G was measured by tandem mass spectrometry in the daughter-ion mode. The limits of quantitation achieved with this method were 1.3 pmol/ml for morphine, 1.5 pmol/ml for normorphine, 1.0 pmol/ml for M6G and 5.4 pmol/ml for M3G in serum or cerebrospinal fluid. The limits of quantitation achieved in urine were 10 pmol/ml for morphine, 20 pmol/ml for normorphine and M6G and 50 pmol/ml for M3G using a sample size of 100 microl. The method described was successfully applied to the determination of morphine and its metabolites in human serum, cerebrospinal fluid and urine in pharmacokinetic and drug interaction studies.

Body Fluids↗
PubMed1999

Pharmacokinetics of dihydrocodeine and its active metabolite after single and multiple oral dosing.

AIMS: The pharmacokinetics of dihydrocodeine (DHC) and its active metabolite dihydromorphine (DHM) were assessed after a single oral dose of DHC and after increasing doses of DHC at steady-state. Methods Twelve healthy male volunteers (18-45 years, CYP2D6 extensive metabolizers (EMs), MR<1 took a single oral dose (s.d.) of DHC 60 mg after breakfast. After 60 h DHC 60 mg was administered twice daily for 3 days, the dose was increased to 90 mg twice daily for 3 days, the final dose of 120 mg was administered twice daily for 3 days (multiple dose: m.d.). Blood sampling and urine collection: during 60 h after s.d. and during 12 h after m.d. Results No significant differences in the area under the curve (AUC) of both, DHC and DHM could be detected after a single oral dose of 60 mg DHC (AUC (0,infinity)) and during steady-state doses of 60 mg DHC (AUC(0,12 h)). During increasing steady-state doses of DHC, the data showed a dose linearity of AUC, maximal serum concentration (Cmax ) and minimal steady-state serum levels (Cssmin) of both, DHC and DHM (P<0.0001), point estimates of DHC dose corrected AUCs were well within the bioequivalence range (60 mg: 0.989; 90%CI 0.951-1. 028, 90 mg: 0.997; 90%CI 0.959-1.036, 120 mg: 0.977; 90%CI 0.940-1. 016). O-demethylation from DHC to DHM remained constant within the increasing steady-state doses of DHC in the 12 extensive metabolizers of CYP2D6. CONCLUSIONS: In the studied dose range (60-120 mg) the pharmacokinetics of DHC and its active metabolite DHM are linear in EMs of CYP2D6.

Administration, Oral↗
PubMed1999

Chronopharmacology of intravenous and oral modified release verapamil.

AIMS: Using a stable isotope technique which allows simultaneous and differential measuring of orally and intravenously administered drugs we compared the pharmacokinetics and pharmacodynamics of unlabelled modified release verapamil p.o. (steady state) and deuterated verapamil i.v. (single dose) following morning and evening administration. METHODS: Twelve female and 12 male healthy volunteers were studied in a randomized, crossover design. During the last day of each treatment period (day 6 and day 10) pharmacokinetics and pharmacodynamics (PR interval) of verapamil were assessed; 1 h before ingestion of a new R/S-verapamil 240 mg modified release formulation (08.00 h vs 20.00 h) a single dose of 10 mg d7-R/S-verapamil was administered intravenously. Serum levels of unlabelled and labelled R/S-verapamil were measured by gas chromatography/mass spectrometry. In selected samples of serum which were chosen at tmin,po and tmax,po the enantiomers were separated by chiral high-performance liquid chromatography in order to calculate R- to S-verapamil serum concentration ratios. RESULTS: We observed no significant differences in pharmacokinetics (AUCpo, Cmax, tmax, CLo, F and R/S enantiomer ratio) between morning and evening treatment with modified release verapamil and there was no influence of time of dosing on mean prolongation of PR interval. AUCiv, CL, Vss and d7-R/d7-S enantiomer ratio following verapamil i.v. did not show circadian variation. t1/2 was slightly but statistically significantly increased after the morning infusion. PR-prolongation was significantly greater after verapamil i.v. in the morning than in the evening. The 90% confidence intervals of the differences between morning and evening administration in AUCpo, Cmax and AUCiv were within the equivalence range of 0.8-1.25. CONCLUSIONS: Time of dosing has no significant influence on pharmacokinetics and pharmacodynamics of this new modified release formulation of verapamil. Circadian variation in presystemic metabolism of verapamil was not observed.

Administration, Oral↗
PubMed1999

A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis.

Numerous spontaneous and experimentally induced mouse mutations develop a hair phenotype, which is often associated with more or less discrete abnormalities in hair follicle development. In order to recognize these, it is critically important to be able to determine and to classify accurately the major stages of normal murine hair follicle morphogenesis. As an aid, we propose a pragmatic and comprehensive guide, modified after previous suggestions by Hardy, and provide a list of easily recognizable classification criteria, illustrated by representative micrographs. Basic and more advanced criteria are distinguished, the former being applicable to all mouse strains and requiring only simple histologic stains (hematoxylin and eosin, Giemsa, periodic acid Schiff, alkaline phosphatase activity), the latter serving as auxiliary criteria, which require a pigmented mouse strain (like C57BL/6J) or immunohistochemistry (interleukin-1 receptor type I, transforming growth factor-beta receptor type II). In addition, we present simplified, computer-generated schematic drawings for the standardized recording and reporting of gene and antigen expression patterns during hair follicle development. This classification aid serves as a basic introduction into the field of hair follicle morphogenesis, aims at standardizing the presentation of related hair research data, and should become a useful tool when screening new mouse mutants for discrete abnormalities of hair follicle morphogenesis (compared with the respective wild type) in a highly reproducible, easily applicable, and quantifiable manner.

Animals↗
PubMed1999

Pharmacokinetics of morphine and its glucuronides following intravenous administration of morphine in patients undergoing continuous ambulatory peritoneal dialysis.

BACKGROUND: Conjugation with glucuronic acid represents the major route of biotransformation of morphine. The glucuronides morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are eliminated via the kidneys. Therefore, chronic renal failure should affect the disposition of M3G and M6G. Numerous patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD) require pain treatment with morphine. There are only limited data available about the disposition of morphine and its active metabolites M6G and M3G in patients on CAPD. We therefore investigated the pharmacokinetics of morphine and its metabolites in CAPD patients. METHODS: This was a single intravenous dose pharmacokinetic study in 10 CAPD patients (1 female, 9 male, age 31-69 years). Morphine-hydrochloride (Mo) (10 mg) was administered intravenously. Serum, urine, and dialysate samples were collected during 24 h. GC-MS-MS and HPLC-MS methods were used to quantify respectively morphine and morphine glucuronides. RESULTS: While systemic clearance of morphine (1246+/-240 ml/min) was in the range observed in patients with normal kidney function, both M3G and M6G showed substantial accumulation. The area under the concentration-time curve (AUC) ratio of M3G:Mo (33.4+/-7.1) and of M6G:Mo (12.2+/-3.2) was 5.5 and 13.5 times higher than in patients with normal kidney function. Renal clearances of morphine, M3G, and M6G (morphine 3.0+/-2.5 ml/min; M3G 3.9+/-2.2 ml/min; M6G 3.6+/-2.2 ml/min) and dialysate clearances (morphine 4.1+/-1.3 ml/min; M3G 3.2+/-0.7 ml/min; M6G 3.0+/-0.8 ml/min) were extremely low. Therefore the accumulation of M6G and M3G is readily explained by kidney failure which is not compensated by CAPD. CONCLUSION: Accumulation of M3G and M6G is due to the substantially lowered clearance by residual renal function and peritoneal dialysis. In view of the accumulation of potential active metabolites, subsequent investigations have to assess the frequency of side-effects in patients on CAPD.

Adult↗
PubMed1999

Consequences of rifampicin treatment on propafenone disposition in extensive and poor metabolizers of CYP2D6.

Propafenone undergoes extensive metabolism both by phase I and phase II enzymes: cytochrome P4502D6 (CYP2D6) dependent polymorphic hydroxylation to its main metabolite 5-OH-propafenone, CYP3A4/1A2 dependent N-dealkylation and further glucuronidation and sulfation. Since CYP2D6 is not inducible by rifampicin, an important drug interaction between rifampicin and propafenone is not to be expected a priori. However, non-CYP2D6-dependent pathways may be induced as a case report described dramatically lowered plasma concentrations of propafenone with loss of dysrhythmia control associated with rifampicin treatment. Therefore, this study aimed to investigate induction properties of rifampicin on propafenone disposition in extensive metabolizers and poor metabolizers of CYP2D6. Six extensive metabolizers and six poor metabolizers ingested 600 mg rifampicin once daily for nine consecutive days. The day before the first rifampicin dose and on the day of the last rifampicin dose each individual received a single intravenous (i.v.) infusion of 140 mg unlabelled propafenone and 2 h later a single dose of 300 mg deuterated propafenone orally (p.o.). During enzyme induction maximum QRS prolongation decreased significantly after propafenone p.o. (21 +/- 7% versus 13 +/- 6% in extensive metabolizers, P < 0.01; 15 +/- 6% versus 9 +/- 6% in poor metabolizers, P < 0.01) and not after propafenone i.v. In parallel, there were no substantial differences in pharmacokinetics of propafenone i.v. by rifampicin. However, bioavailability of propafenone dropped from 30 +/- 15% to 10 +/- 8% in extensive metabolizers (P < 0.01) and from 81 +/- 6% to 48 +/- 8% in poor metabolizers (P < 0.001). Following propafenone p.o. clearances through N-dealkylation (4.1 +/- 2.1 ml/min versus 23.5 +/- 12.6 ml/min in extensive metabolizers, P < 0.01; 3.4 +/- 1.3 ml/min versus 16.0 +/- 5.5 ml/min in poor metabolizers, P < 0.001) and glucuronidation (123 +/- 48 ml/min versus 457 +/- 267 ml/min in extensive metabolizers, P < 0.05; 43 +/- 9 ml/min versus 112 +/- 34 ml/min in poor metabolizers, P < 0.01), but not 5-hydroxylation increased regardless of phenotype indicating substantial enzyme induction. Clearances to propafenone sulfate and conjugates of 5-OH-propafenone were significantly enhanced by rifampicin treatment in poor metabolizers (P < 0.01). Thus, induction of both phase I pathways (CYP3A4/1A2) and phase II pathways (glucuronidation, sulfation) of propafenone by rifampicin resulted in a clinically relevant metabolic drug interaction which was more pronounced in extensive metabolizers than in poor metabolizers with regard to percentage decrease in bioavailability of propafenone.

Administration, Oral↗
PubMed1998

The anagen hair cycle induces systemic immunosuppression of contact hypersensitivity in mice.

Contact hypersensitivity (CHS) to picryl chloride (PCl) is depressed in C57BL/6 mice when CHS is induced via early anagen skin. We have now further dissected this phenomenon in vivo. The elicitation phase for CHS was suppressed when anagen was induced 4 days after PCl sensitization of telogen animals. Sensitization of mice via abdominal skin with all hair follicles in telogen, and back skin follicles in anagen, significantly reduced the magnitude of the ear swelling response. Consecutive applications of two sensitizing doses of hapten, first on induced anagen back skin and then on telogen abdominal skin 7 days later, failed to induce tolerance. Furthermore, spleen cell transfer of sensitized anagen mice into telogen mice did not inhibit CHS response in the recipients. The current study suggests that a temporary state of systemic hyporesponsiveness, mediated, e.g., by hair cycle-dependent production of immunosuppressive cytokines rather than hapten-specific T suppressor cell activities, plays a critical role.

Animals↗
PubMed1998

Focal hyperhidrosis: effective treatment with intracutaneous botulinum toxin.

OBJECTIVE: To evaluate the effect of intracutaneous injections of botulinum toxin type A on excessive focal hyperhidrosis. DESIGN: Therapeutic before-and-after trial over 4 months. SETTING: Neurological and dermatological university departments. PATIENTS: Eleven patients with excessive axillary, palmar, or plantar hyperhidrosis fulfilling the following criteria: (1) local and systemic drug therapy had failed to improve their symptoms; (2) the patients were severely disabled with respect to their occupation and social activities; and (3) a successful treatment by botulinum toxin would obviate the need for destructive surgical procedures. INTERVENTIONS: Three mouse units of botulinum toxin (Botox) per 4-cm2 skin area was injected intracutaneously in 16 axillae, 8 palms, and 2 soles. MAIN OUTCOME MEASURES: Reduction of hyperhidrosis as documented by the Minor iodine-starch test and gravimetrical assessment of local spontaneous sweat production measured over 1 minute. RESULTS: In all patients, botulinum toxin completely abolished sweating in the injected areas (P<.001) within 3 to 7 days. No relevant adverse effects occurred and no clinical recurrence of hyperhidrosis was observed within the follow-up period of up to 5 months. Occasionally, subclinical reactivation of sweat gland function was observed 4 months after treatment. CONCLUSIONS: Intracutaneous botulinum toxin seems preferable to any hitherto used conservative or surgical procedures and may become the therapy of choice in pathological focal hyperhidrosis.

Adult↗
PubMed1998

Ocular pharmacokinetics of verapamil in rabbits.

Previously, it had been demonstrated that cataract in diabetic rats can be prevented by systemical administration of the calcium channel blocker verapamil. In addition to that, 0.125% verapamil eye drops were found to significantly reduce the intraocular pressure in ocular hypertensive human subjects. The purpose of this study was to investigate the ocular penetration and elimination of verapamil after topical administration of the drug in rabbits. Two drops of a 0.125% aqueous solution of RS-verapamil hydrochloride (corresponding to a total dose of 125 microg RS-verapamil hydrochloride) were administered into the conjunctival sac. Aqueous humor and blood samples were taken at different times after administration and analysed for drug concentration by combined gas chromatography-mass spectroscopy. Following the instillation of 0.125% verapamil eye drops in a total dose of 125 microg RS-verapamil, mean (+/- SEM) aqueous humor peak levels of 1607 +/- 272 ng/ml were achieved after 20 min. Mean half-life for the elimination from the aqueous humor was 33 min. Topical application of verapamil produced very low serum peak concentrations (10.5 +/- 1.3 ng/ml). The results of our study demonstrate that topically administered verapamil readily penetrates into the anterior chamber leading to aqueous humor drug levels in the microM range without producing serum levels that are high enough to cause cardiovascular side effects.

Administration, Topical↗
PubMed1998

[Linear and whorled nevoid hypermelanosis. Case report and review of the literature].

A 7 year old boy presented with linear and whorled nevoid hypermelanosis (LWNH). This entity, delineated in 1988, is characterized by streaked or whorled, frequently reticulate hyperpigmented lesions following the lines of Blaschko without preceding inflammation and without atrophy. The age of onset is usually within the first 2 years of life. Histologically, there is a mild basal cell hyperpigmentation with prominent melanocytes. In contrast to earlier reports, we observed some melanophages in the upper dermis. Associated abnormalities have been reported in a few patients, but were absent in our case. We present the clinical features, diagnostic criteria and differential diagnosis of this rare entity. Apparently, our patient represents the first case of LWNH in the German literature.

Basement Membrane↗
PubMed1998

Characterization of the thromboxane synthase pathway product 12-oxoheptadeca-5(Z)-8(E)-10(E)-trienoic acid as a thromboxane A2 receptor antagonist with minimal intrinsic activity.

Thromboxane synthase forms thromboxane (TX) A2 and 12(S)-hydroxyheptadeca-5(Z)-8(E)-10(E)-trienoic acid (HHT) at equimolar amounts. Twelve-oxoheptadeca-5(Z)-8(E)-10(E)-trienoic acid (Oxo-HT) is the primary metabolite of HHT and has been described to be an inhibitor of platelet aggregation. Functional studies, Schild analysis and competitive binding studies were performed to clarify its mode of action. Oxo-HT was prepared biosynthetically as well as chemosynthetically, purified and characterized by gas chromatography and mass spectrometry. Platelet activation was assessed by determination of shape change, aggregation, fibrinogen binding and P-selectin expression using optical aggregometry and flow cytometry. Oxo-HT 0.1 nM to 50 microM did not induce platelet activation. Furthermore, it had no effect on platelet activation induced by thrombin, ADP or PAF. In contrast, Oxo-HT inhibited platelet aggregation, fibrinogen binding and P-selectin expression induced by U46619 in a competitive manner. Schild analysis for U146619-induced fibrinogen binding and P-selectin expression revealed pA2 values of 6.1 and 6.6, respectively, which correspond to Kd values of approximately 0.8 microM and 0.3 microM, respectively. Oxo-HT also inhibited U46619 induced shape change (IC50 is approximately equal to 10 microM). However, Oxo-HT over a concentration range of 0.1-1 microM enhanced the partial shape change induced by low concentrations of U46619. Thus Oxo-HT seems to possess a minimal agonistic potential, which alone is not sufficient to trigger a platelet activation but can enhance low levels of platelet activation. Oxo-HT blocked the binding of [3H]SQ 29548 in a concentration-dependent manner, whereas HHT did not displace [3H]SQ 29548. The Kd of Oxo-HT determined from competition binding studies was 7.7 microM, about 10-25-fold higher than the apparent Kd determined by Schild analysis. This discrepancy might be due to a desensitization of the TXA2 receptor triggered by the minimal intrinsic activity of Oxo-HT. We conclude that Oxo-HT is a naturally occurring specific TXA2 receptor antagonist with minimal intrinsic activity. Oxo-HT may contribute to the regulation of TXA2-induced platelet activation in vivo.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

MHC class I expression in murine skin: developmentally controlled and strikingly restricted intraepithelial expression during hair follicle morphogenesis and cycling, and response to cytokine treatment in vivo.

Hair bulb keratinocytes generate one of the few "immune privileged" tissue compartments of the mammalian organism by suppressing classical MHC class I (MHC Ia) antigens. Expression of non-classical MHC class I (MHC Ib) antigens in the follicle has been found, but only in its distal epithelium. Here, we have defined when during murine hair follicle morphogenesis these peculiar MHC Ia and Ib expression patterns are established, how they change during the murine hair cycle, and how different MHC I modulatory agents alter follicular MHC Ia and Ib expression in vivo. During neonatal hair follicle morphogenesis in C57BL/6 mice, distal follicle keratinocytes began to express MHC Ia (H2b) only late in development. The MHC Ib antigens, Qa-1 and Qa-2, did not become visible until the initiation of follicle cycling, with Qa-1 expression being more widespread than that of Qa-2. H2b, Qa-1, and TAP-1 immunoreactivity on previously negative keratinocytes of the proximal anagen hair bulb was upregulated by intradermal injection of the proinflammatory cytokine interferon-gamma, but not by tumor necrosis factor-alpha or interleukin-1beta. Injection of the reportedly MHC class I downregulating agents interleukin-10, insulin-like growth factor-1, transforming growth factor-beta, alpha-melanocyte stimulating hormone, or dexamethasone, however, all failed to downregulate constitutive or interferon-gamma-induced follicular MHC Ia expression. This shows that the hair follicle is a previously unrecognized site of Qa-1 expression and that interferon-gamma is a key regulator of follicular MHC I expression in vivo. It also suggests that the developmental and immunologic controls of MHC I expression by follicle keratinocytes differ from those of other epithelial cells.

Animals↗
PubMed1998

Generation and cyclic remodeling of the hair follicle immune system in mice.

In this immunohistomorphometric study, we have defined basic characteristics of the hair follicle (HF) immune system during follicle morphogenesis and cycling in C57BL/6 mice, in relation to the skin immune system. Langerhans cells and gammadelta T cell receptor immunoreactive lymphocytes were the predominant intraepithelial hematopoietic cells in neonatal mouse skin. After their numeric increase in the epidermis, these cells migrated into the HF, although only when follicle morphogenesis was almost completed. In contrast to Langerhans cells, gammadelta T cell receptor immunoreactive lymphocytes entered the HF only via the epidermis. Throughout HF morphogenesis and cycling, both cell types remained strikingly restricted to the distal outer root sheath. On extremely rare occasions, CD4+ or CD8+ alphabetaTC were detected within the HF epithelium or the sebaceous gland. Major histocompatibility complex class II+, MAC-1+ cells of macrophage phenotype and numerous mast cells appeared very early on during HF development in the perifollicular dermis, and the percentage of degranulated mast cells significantly increased during the initiation of synchronized HF cycling (first catagen). During both depilation- and cyclosporine A-induced HF cycling, the numbers of intrafollicular Langerhans cells, gammadelta T cell receptor immunoreactive lymphocytes, and perifollicular dermal macrophages fluctuated significantly. Yet, no numeric increase of perifollicular macrophages was detectable during HF regression, questioning their proposed role in catagen induction. In summary, the HF immune system is generated fairly late during follicle development, shows striking differences to the extrafollicular skin immune system, and undergoes substantial hair cycle-associated remodeling. In addition, synchronized HF cycling is accompanied by profound alterations of the skin immune system.

Animals↗
PubMed1998

Clusters of perifollicular macrophages in normal murine skin: physiological degeneration of selected hair follicles by programmed organ deletion.

In back skin sections from adolescent C57BL/6 mice, regularly distributed, perifollicular inflammatory cell clusters (PICC) were found located around the distal noncycling portion of about 2% of all hair follicles examined. The PICC and the affected hair follicles were characterized during spontaneously developed or induced hair cycle stages, using antibodies against MHC Class II, F4/80, ER-MP23, NLDC 145, CD4, CD8, gammadeltaTCR, IL-1 receptor, and ICAM-1. PICC consisted predominantly of macrophages (MAC), accompanied by a few CD4+ cells, whereas gammadeltaTCR+ and CD8+ cells were absent. During anagen and catagen, some of the PICC+ hair follicles showed variable degenerative phenomena reminiscent of scarring alopecia: thickened basement membrane, ectopic MHC II expression, MAC infiltration into the follicle epithelium, and signs of keratinocyte apoptosis. Loss of distal outer root sheath keratinocytes was detected in 10% of PICC+ hair follicles (0.2% of all hair follicles). Because PICC were located in the vicinity of the bulge region, MAC-dependent damage to follicle stem cells might eventually lead to follicle degeneration. These perifollicular MAC clusters around selected hair follicles may indicate the existence of a physiological program of MAC-dependent controlled follicle degeneration by which damaged or malfunctioning follicles are removed by programmed organ deletion (POD).

Animals↗