• infrared;
  • matrix metalloproteinases;
  • mitogen-activated protein kinases;
  • photoaging


  1. Top of page
  2. Abstract
  3. Characteristics and sources of IR radiation
  4. Biological effects of IR radiation
  5. Conclusions and future directions
  6. References

Human skin is exposed to infrared (IR) radiation (760 nm–1 mm) from natural as well as artificial sources that are increasingly used for cosmetic or medical purposes. Epidemiological data and clinical observations, however, indicate that IR radiation cannot be considered as totally innocuous to human skin. In particular, IR radiation, similar to ultraviolet radiation, seems to be involved in photoaging and potentially also in photocarcinogenesis. The molecular consequences resulting from IR exposure are virtually unknown. Recent studies, however, have begun to shed light on the basic molecular processes such as cellular signal transduction and gene expression triggered by exposure to IR radiation. In response to IR irradiation, mitogen-activated protein kinase signaling pathways were activated mediating the upregulation of matrix metalloproteinase-1 expression. This previously unrecognized molecular ‘IR response’ shows that IR radiation is capable of specifically interfering with cellular functions and provides a molecular basis for biological effects of IR on human skin.

The human skin as the organism's outermost barrier is in direct contact with environmental factors such as solar radiation. The damaging effects of ultraviolet (UV) radiation on human skin were the major interest of photobiological research in the past. Epidemiological and experimental data indicate that in addition to causing acute reactions such as sunburn and immune suppression, chronic exposure to UVA and UVB is a critical risk factor for premature aging of skin – photoaging – and development of skin cancer – photocarcinogenesis. Over the last several years, remarkable progress has been made in understanding the underlying molecular and biochemical mechanisms. In response to UV radiation, cellular signal transduction pathways initiated at cell surface receptors are activated, resulting in a specific pattern of target gene expression mediating the UV damage to human skin. Moreover, reactive oxygen species (ROS) generated photochemically by UV were identified to initiate these molecular processes.

In marked contrast to the detailed analysis of the UV response, only little is known about the biological effects of infrared (IR) radiation, although human skin is increasingly exposed to IR from several natural as well as artificial sources. IR, similar to UV radiation, is likely to exert biologic effects on human skin. Accordingly, epidemiological data and clinical reports point to its ability to cause and enhance actinic skin damage such as premature aging and carcinogenesis, implying that IR is not generally innocuous to human skin (1, 2). However, IR radiation is increasingly and uncritically used for cosmetic and wellness purposes. Apart from this, IR radiation is used as a therapeutic option in the treatment of several different disease entities such as autoimmunity and inflammation (3, 4), malignant diseases (5–8) and wound healing disorders (9–11).

Here, we present an overview of our current understanding of the biological effects of IR radiation on human skin based on epidemiological and experimental studies. In particular, recent studies are discussed that have begun to identify the molecular response mechanisms to IR exposure.

Characteristics and sources of IR radiation

  1. Top of page
  2. Abstract
  3. Characteristics and sources of IR radiation
  4. Biological effects of IR radiation
  5. Conclusions and future directions
  6. References

Electromagnetic radiation is classified into different spectral regions such as X-rays, UV, visible and IR radiation. IR radiation ranging from 760 nm to 1 mm is non-ionizing radiation located ‘below the red’, i.e. adjacent to the red part of the visible radiation range and extending up to the microwave range (Fig. 1).


Figure 1.  Electromagnetic spectrum with spectral regions and photon energy.

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The IR spectral region is arbitrarily divided according to wavelength into the subregions IR-A (760–1400 nm), IR-B (1400–3000 nm) and IR-C (3000 nm–1 mm), or alternatively into near IR (760–3000 nm), middle IR (3000–30 000 nm) and far IR (30 000 nm–1 mm). This subdivision corresponds in part with the biological effects of IR such as the wavelength-dependent absorption in different skin layers (Fig. 2). The depth of penetration into the skin and subcutaneous tissues decreases with increasing wavelength in the IR spectral region. Short wavelength in the IR-A range reaches the subcutaneous tissue without increasing the surface temperature of the skin markedly, whereas IR-C is absorbed completely in the epidermal layers and causes an increase in skin temperature resulting in thermal sensation ranging from pleasant warmth to thermal burn.


Figure 2.  Wavelength-dependent absorption of IR by human skin. The amount of radiation absorbed at different layers of the skin is shown as percent of total radiation absorbed. The wavelengths examined were 1000 nm for IR-A, 1400 nm for IR-B and 3000–6000 nm for IR-C (57).

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The photon energy of electromagnetic radiation is inversely related to the wavelength. Thus, radiation in the IR-A range is associated with about a third (1.9×10−19 J/photon) of the energy associated with UVA/B radiation (5.6–6.6×10−19 J/photon) (12). Consequently, most photochemical reactions are induced by UV radiation, whereas IR typically induces molecular vibrations and rotations causing an increase in temperature. However, this modification of the vibrational and rotational energy state of molecules by IR may influence the photochemical reactions induced by UV and may thus enhance the damaging effects of UV on human skin.

The major natural source of daily IR exposure on earth is the sun. The solar spectrum reaching the earth's surface ranges from 290 to 3000 nm and includes UV radiation (UVB, 290–320 nm; UVA, 320–400 nm), visible radiation (400–760 nm) and IR radiation (760–3000 nm). The corresponding solar energy is 6.8% in the UV range (0.5% UVB, 6.3% UVA), 38.9% in the visible range and the IR spectral range constitutes about 54.3% of total solar irradiance (12). Thus, humans are exposed to significant amounts of IR radiation, with an average dose of 75 J/cm2/h (summertime, Munich, Germany). In fact, because of the increased popularity of outdoor activities and the use of sunscreens without protection in the IR range, exposure of human skin to solar IR is most likely increasing.

In addition, artificial solar irradiation devices frequently used for cosmetic purposes emit large quantities of IR radiation. As a novel trend, IR irradiation devices are employed for wellness purposes, including anti-aging therapies and other lifestyle-driven, scientifically unjustified and unproven modalities.

Thus, IR radiation is a significant environmental factor with increasing relevance for human health, in general, and the integrity of human skin, in particular.

Biological effects of IR radiation

  1. Top of page
  2. Abstract
  3. Characteristics and sources of IR radiation
  4. Biological effects of IR radiation
  5. Conclusions and future directions
  6. References

As a result of chronic exposure to UV radiation, affected skin areas show signs of epidermal and dermal damage such as hyperkeratosis, keratinocyte dysplasia and dermal elastosis clinically presenting as photoaged skin with actinic or solar keratosis. These precancerous lesions show an increased risk for the development of squamous cell carcinoma (SCC). Similar long-term cutaneous effects can be observed in skin areas after chronic exposure to heat and IR radiation, which have been well described over the last several decades. Repeated exposure to sources of heat and IR such as fires and stoves results in a skin lesion described as erythema ab igne (13). This dermatosis is clinically characterized by a reticular hyperpigmentation and teleangiectasia accompanied histologically by epidermal atrophy, vasodilation, and dermal melanin and hemosiderin deposits. After many years, these lesions may develop the histological characteristics of thermal keratoses such as hyperkeratosis, keratinocyte dysplasia and dermal elastosis which are similar to the changes occurring in actinically damaged skin (14). As with actinic keratoses, thermal keratoses are precancerous lesions showing epidermal dysplasia, which may develop into invasive SCC. There are several reports of carcinomas arising from heat-induced erythema ab igne (1, 15–19). Clinical observations and results from epidemiological studies over the last few decades thus indicate that IR and heat radiation are involved in skin carcinogenesis and cannot be considered as completely harmless to human skin.

In accordance with these observations are results from experimental studies on the contribution of IR radiation to actinic skin damage. Already 20 years ago it was reported for the first time that IR irradiation caused skin changes that were similar to those found in solar UV radiation-induced elastosis (20). Chronic IR exposure of albino guinea-pigs resulted in an early and cumulative increase in the number and thickness of elastic fibers and the production of dense accretions of fine, feathery fibers as detected histologically. In addition, there was a large increase in ground substance, comparable to that observed in actinically damaged human skin. Consecutive exposure of animals to UV and IR resulted in enhanced elastic fiber deposition in the dermis and thus enhanced dermal damage induced by UV. In conclusion, this study, for the first time, provided experimental data indicating the capability of IR to induce dermal damage resembling solar elastosis of photodamaged skin.

As with IR-induced photoaging, the carcinogenic potential of heat and IR radiation is supported by early experimental studies. In particular, in 1943, the influence of temperature on UV-induced carcinogenesis was studied in mice (21). Skin tumors in mice appeared faster after irradiation with the full lamp spectrum containing UV, visible and IR compared to irradiation with UV (280–340 nm) alone. The authors concluded that increased tumorigenesis was a result of the heat produced by the lamp. In a different study, Freeman and Knox (22) observed that UV injury in animals was enhanced by elevated temperature. In a more recent study, it was shown that increased temperature led to a tumorigenic conversion of the keratinocyte line HaCaT via induction of DNA strand breaks (23). Although several epidemiological and experimental studies point to the involvement of IR radiation in skin aging and carcinogenesis, the basic molecular mechanisms underlying the biological consequences of IR exposure remain largely unknown.

Molecular response mechanisms

Premature aging of the skin as a long-term consequence of repeated UV exposure presents clinically with wrinkle formation, loss of skin tone and pigmentation abnormalities, and shows an increased risk for development of skin neoplasias (24–26). Degradation of collagen and accumulation of abnormal elastic fibers in the dermal connective tissue is the histological hallmark of photodamaged skin. The underlying pathophysiological mechanisms have been investigated intensively during the last decade. Exposure of human skin to UVA and UVB induces the expression of several target genes, among them matrix metalloproteinases (MMPs) (27, 28). The MMPs are zinc-dependent endopeptidases responsible for the degradation of extracellular matrix components such as collagen and elastin. Their activity is of critical relevance in biological processes such as embryonic development, angiogenesis and wound healing. Under physiological conditions, MMPs are part of a coordinate network and are precisely regulated by their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs). However, the unbalanced activity of MMPs with excessive proteolysis is a major pathophysiological factor in several diseases such as rheumatic diseases, hepatic cirrhosis, tumor invasion and metastasis (29). Exposure of human skin to UV radiation induces the expression of MMPs, resulting in cleavage of fibrillar collagen, and thus impairs the structural integrity of the dermis. Insufficient repair and repeated exposure to UV radiation lead to accumulation of connective tissue damage, which is a key pathophysiological factor in photoaging (26, 27, 30, 31).

The described actinic damage to human skin is mediated by cellular signaling pathways regulating the expression of target genes. Cells respond to UV radiation with activation of several protein kinase signaling cascades such as the mitogen-activated protein kinases (MAPKs) initiated at cell surface receptors (32). Three distinct MAPK pathways have been studied intensively: the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway (Raf[RIGHTWARDS ARROW]MEK1/2[RIGHTWARDS ARROW]ERK1/2), and the c-Jun N-terminal kinase (MEKK1/3[RIGHTWARDS ARROW]MKK4/7[RIGHTWARDS ARROW]JNK1/2/3) and p38 (MEKK[RIGHTWARDS ARROW]MKK3/6[RIGHTWARDS ARROW]p38 α–δ) pathways also termed stress-activated protein kinases (SAPKs). The ERK1/2 pathway is primarily induced by mitogens such as growth factors, whereas the SAPK pathways are predominantly induced by inflammatory cytokines as well as environmental stress such as UV, heat and osmotic shock. Activated MAPKs translocate to the nucleus, where they phosphorylate and activate transcription factors such as c-Jun, c-Fos, ATF-2 and ternary complex factors (TCF) leading to the formation and activation of homo- or heterodimeric forms of the transcription factor AP-1 (33–35). The promoter region of MMP-1 carries multiple AP-1-binding sites (36, 37), transactivation of which by binding active AP-1 leads to enhanced MMP-1 gene expression in response to UVB (28, 38) and UVA (39). Photochemically generated ROS such as singlet oxygen and hydrogen peroxide were identified as the initial triggers of the molecular UV response (31, 40–43). Several recent studies indicate that ROS causes an inactivation of protein–tyrosine phosphatases (PTPs) by oxidizing the conserved cysteine residue in the active sites of PTPs and thereby causing a net increase in kinase phosphorylation/activation (44–47). Redox regulation of signaling processes also seems to be involved in UV-induced signaling: photochemically generated ROS were shown to inactivate PTPs enabling the activation of signaling pathways (48, 49).

In contrast to the detailed characterization of the UV response, only little is known about the molecular effects and biological consequences of IR irradiation on human skin. In recent studies, we have observed that in response to IR-A, dermal fibroblasts showed a time- and dose-dependent increase in collagenase (MMP-1) expression whereas the expression of its endogenous inhibitor, TIMP-1, was not increased (50). In terms of physiological relevance, it is important to note that the IR-A doses employed in this study correspond very well to environmental doses. The lowest dose of 200 J/cm2, which was observed to cause a 2.5-fold increase of MMP-1 mRNA, can be acquired during summer time in southern Germany after a 2.5 h exposure to solar radiation (calculations based on data obtained from Deutscher Wetterdienst, Potsdam, Germany). In conclusion, the unbalanced upregulation of MMP-1 indicates the possibility that IR-A-irradiated fibroblasts have an increased capacity to degrade dermal collagen fibers proteolytically. These findings therefore offer a possible molecular mechanism to explain previous observations indicating that IR exposure of guinea-pigs caused skin changes similar to those found in solar elastosis and enhanced UV-induced dermal damage (20).

In addition, this study began to identify the cellular signaling pathways that mediate MMP-1 expression. Similar to UVB and UVA, exposure of dermal fibroblasts to IR-A leads to a rapid activation of ERK1/2 and p38-MAPK signaling cascades. Whereas p38 activation was markedly decreased 15 min after irradiation, activation of ERK1/2 sustained for up to 120 min (50). This activation pattern, however, is distinct from that reported for UVB and UVA. Exposure to UVA and singlet oxygen shows no phosphorylation and activation of ERK1/2 in human skin fibroblasts (51). Exposure of human keratinocytes to UVB leads to a more prolonged activation of p38, which remains activated for 2 h, and a rapid activation of ERK1/2, which markedly decreases after 15 min (43). Interestingly, the IR-A-induced activation of the ERK1/2 signaling pathway was functionally involved in MMP-1 expression in response to IR. The inhibition of this pathway by employing a specific pharmacological compound prevented the IR-A-induced MMP-1 expression, thus indicating that IR-A induces MMP-1 expression via activation of the ERK1/2 signaling cascade (Fig. 3).


Figure 3.  Activation of MAPK signaling pathways and upregulation of MMP-1 expression by IR-A. In response to IR-A exposure, p38-MAPK and ERK1/2 are activated in human dermal fibroblasts. Activated MAPK translocate to the nucleus where they phosphorylate and activate transcription factors (e.g. AP-1). Upregulation of MMP-1 expression resulting in an increase of MMP-1 mRNA and protein is mediated by activation of the MEK/ERK1/2 signaling pathway in response to IR-A (50).

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Since MAPKs are involved in transcriptional regulation of a multitude of genes, it is very likely that IR radiation is able to influence the expression of several genes via activation of MAPK signaling pathways. Furthermore, IR radiation may also activate other signaling cascades regulating gene expression rather than exclusively influencing MAPK pathways.

These results indicate that IR is capable of eliciting a molecular response in dermal fibroblasts similar to that induced by UV radiation. We therefore propose the term ‘IR response’ to emphasize the ability of IR to influence specifically cellular functions such as signal transduction and gene expression.

These findings are in accordance with results from previous studies reporting an influence of IR on cellular functions such as gene expression and proliferation. Danno and Sugie (52) could show that epidermal proliferation, Langerhans cell density and contact hypersensitivity reaction in mice were decreased after IR irradiation. The study from Applegate et al. (53) showed an influence of IR on protein expression by demonstrating an increase in ferritin expression after IR irradiation of keratinocytes and fibroblasts in vivo and in vitro, respectively. Induction of the putative defense system of ferritin in human skin after exposure to IR could be suggestive of oxidative processes triggered by IR.

The gene-regulatory function of IR was further indicated in a study by Danno et al. (9) showing an increased TGF-β1 and MMP-2 expression after IR irradiation of human keratinocytes, endothelial cells and fibroblasts, respectively.

In contrast to potentially detrimental effects, IR radiation might also have beneficial effects on human skin. Accordingly, IR has been reported to confer protection against UV-induced cytotoxicity. Irradiation of skin with UVB induces keratinocyte apoptosis, which can be detected histologically as sunburn cells in the epidermis. Sunburn cell formation in response to UVB exposure was significantly reduced after preirradiation with IR (54). Another study showed that UVA- and UVB-induced cell death of human skin fibroblasts was decreased by IR pretreatment (55). This protective effect was detected almost immediately after IR irradiation with a maximum at 24 h. However, no protection against UVA-induced lipid peroxidation could be detected.

The photophysical and photochemical mechanisms that mediate the described molecular effects and biological consequences of IR irradiation can range from production of heat via internal conversion of electronic into vibrational energy to chemical modifications of certain photoacceptors. Some experimental data indirectly imply an involvement of oxidative processes triggered by IR radiation. In addition to the above-mentioned expression of ferritin after IR exposure, cytochrome c oxidase, an enzyme of the respiratory chain located in the mitochondrial inner membrane, was shown to absorb energy in the near-IR range, thereby altering the redox status of respiratory chain constituents that might lead to the generation of ROS such as singlet oxygen, superoxide anion radical and hydrogen peroxide (56). However, the exact photophysical and photochemical mechanisms triggered by IR are unknown so far, and future studies will have to reveal the photochemical details in order to obtain a scientific basis for the development of strategies to prevent IR-induced skin damage.

Conclusions and future directions

  1. Top of page
  2. Abstract
  3. Characteristics and sources of IR radiation
  4. Biological effects of IR radiation
  5. Conclusions and future directions
  6. References

The influence of IR radiation on biological processes in human skin has become obvious from numerous studies over the last several years. Similar to UV, chronic exposure to IR seems to be involved in photoaging and photocarcinogenesis. In addition to this, IR may also have beneficial effects on human skin such as induction of stress resistance. However, the factors that determine the specific biological outcome elicited by IR exposure remain uncharacterized. The underlying molecular mechanisms activated by IR radiation have just begun to be identified. Further analysis of the molecular ‘IR response’ and the photophysical and photochemical reactions induced by IR should provide valuable information to reconcile the diverse influences of IR on cellular functions with effects on aging, tumor formation and stress resistance. These studies may also reveal novel therapeutic applications of IR radiation in clinical medicine. In addition, it is of practical importance to evaluate the relevance of IR in comparison to UV for solar radiation-induced effects on extracellular matrix turnover, immune function and the stress response in vivo. Moreover, the results provided by these studies should allow the development of photoprotective strategies against unwanted IR effects.


  1. Top of page
  2. Abstract
  3. Characteristics and sources of IR radiation
  4. Biological effects of IR radiation
  5. Conclusions and future directions
  6. References
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